Novel derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same

ABSTRACT

Provided are a compound having a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same and a use thereof, where the compound having a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof has an inhibitory activity against glucosylceramide synthase (GCS), and therefore can be usefully applied for preventing or treating various diseases associated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachs disease, Parkinson&#39;s disease, etc.

TECHNICAL FIELD

The present invention relates to a novel compound having an inhibitoryactivity against glucosylceramide synthase (GCS), i.e., derivativeshaving a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceuticallyacceptable salt thereof, a process for the preparation thereof, apharmaceutical composition comprising the same and a use thereof.

BACKGROUND ART

Lysosomal storage disorders (LSDs) are the metabolic disorders thatresult from genetic lack or deficiency of certain enzymes in lysosomes.LSDs exhibit various pathological symptoms throughout the body, as thenon-metabolized or non-degraded substrates are accumulated. Currently,about 50 types of LSDs are known and are largely classified into thediseases such as mucopolysaccaridose, oligosaccharidosis, andsphingolipidoses, depending on the substances accumulated.

Among the diseases, sphingolipidoses, which are a class of glycolipidstorage disorders relating to sphingolipid metabolism, show pathologiesdue to the accumulation of various membrane glycosphingolipids (GSLs),such as glucosylceramide, trihexocylceramide, etc. For example, when theenzymes related to sphingolipid metabolism, such as beta-glucosidase,alpha-galactosidase, etc., do not have normal activity, the substratesthereof (e.g., glucosylceramide, trihexocylceramide, etc.) areaccumulated, thereby exhibiting various pathologies, such as Gaucherdisease, Fabry disease, etc.

There are known two types of therapies for the LSDs. The first method isto replace or supplement the insufficient or deficient metabolicenzymes. Although such an enzyme replacement therapy (ERT) is safe andeffective, periodic intravenous administrations of the related enzyme(s)are required; the dose thereof should be adjusted according to theenzyme reaction(s); and the costs thereof are relatively high.Especially, since it is difficult to distribute the enzyme(s) toward thenervous system, the ERT does not show satisfactory efficacy in thetreatment of symptoms related to the nervous system. In addition, thereis also the problem that autoantibodies against the administeredenzyme(s) are frequently generated.

The second method is a substrate reduction therapy (SRT) for inhibitingthe syntheses of accumulated substrates. Glucosylceramide synthase (GCS)(also referred to as “UDP-glucose: ceramide glycosyltransferase”,“UDP-glucose: N-acylsphingosine D-glucosyltransferase”, or “EC2.4.1.80”), which is an enzyme involved in sphingolipid metabolism, isinvolved in the reaction of ceramide with glucose to produceglucosylceramide. The resulting glucosylceramide is converted intovarious GSLs. Glucosylceramide synthase (GCS) inhibitors inhibit theactivity of GCS, thereby reducing the production of glucosylceramide inthe body and preventing abnormal accumulation of glycolipids, such astrihexocylceramide, GM1, and GM2, in cells or organs.

As such, GCS inhibitors inhibit the activity of GCS to prevent theaccumulation of glycolipids and thus may be usefully applied to thetreatment of lysosomal storage disorders, especially glycolipid storagedisorders, such as GM1 gangliosidosis, Tay-Sachs disease, Sandhoffdisease, Gaucher disease, Fabry disease, Niemann-Pick disease (types Aand B), metachromatic leukodystrophy, Krabbe disease, etc. GCSinhibitors may be also used in the treatment of the secondary diseasesassociated with glycolipid storage, such as Niemann-Pick disease (typeC), mucopolysaccharidosis, and mucolipidosis type IV (see, Chen C S, etal., Abnormal transport along the lysosomal pathway in mucolipidosis,type IV disease Proc Natl Acad Sci USA. 1998 May 26; 95(11):6373-8; andGoodman L A, et al., Ectopic dendrites occur only on cortical pyramidalcells containing elevated GM2 ganglioside in alpha-mannosidosis, ProcNatl Acad Sci USA. 1991 Dec. 15; 88(24):11330-4). In addition, it hasbeen reported to be useful in the treatment of diseases associated withthe accumulation of glycolipids, such as renal hypertrophy (e.g.,diabetic kidney disease); hyperglycemia or hyperinsulinemia; cancerswith abnormal glycolipid synthesis; infectious diseases caused by theorganisms using cell-surface glycolipids as a receptor; infectiousdiseases where the synthesis of glucosylceramide is essential orimportant; diseases in which excessive glycolipid synthesis occurs(e.g., atherosclerosis, polycystic kidney disease, and renalhypertrophy); neurological disorders and/or damages associated with thereplenishment and activity of macrophages (e.g., Alzheimer's disease,epilepsy, stroke, spinal cord diseases, Parkinson's disease, etc.);inflammatory diseases or disorders (e.g., rheumatoid arthritis, Crohn'sdisease, asthma, sepsis); and diabetes and obesity (see, WO2006/053043). And, overexpression of GCS interferes withceramide-induced apoptosis (see, Liu Y Y, et al., Uncoupling ceramideglycosylation by transfection of glucosylceramide synthase antisensereverses adriamycin resistance, J Biol Chem. 2000 Mar. 10;275(10):7138-43). Therefore, GCS inhibitors may be useful for treatingproliferative diseases, such as cancer, by inducing apoptosis indiseased cells.

Various studies have been conducted to develop GCS inhibitors. Forexample, various compounds having an inhibitory activity against GCShave been disclosed in WO 2005/068426, WO 2006/053043, WO 2008/150486,WO 2009/117150, WO 2010/014554, WO 2014/043068, etc.

DISCLOSURE Technical Problem

The present inventors have found that a derivative having a 6,6-fusedbicyclic moiety, i.e., a 1,2,3,4-tetrahydronaphthalene moiety, orpharmaceutically acceptable salt thereof has an excellent inhibitoryactivity against glucosylceramide synthase (GCS).

Therefore, the derivative having a 1,2,3,4-tetrahydronaphthalene moietyor pharmaceutically acceptable salt thereof can be usefully applied forpreventing or treating various diseases associated with GCS, such asGaucher disease, Fabry disease, Tay-Sachs disease, Parkinson's disease,etc.

Therefore, the present invention provides the above derivative having a1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable saltthereof, a process for the preparation thereof, a pharmaceuticalcomposition comprising the same, and a use thereof.

Technical Solution

According to an aspect of the present invention, there is provided aderivative having a 1,2,3,4-tetrahydronaphthalene moiety orpharmaceutically acceptable salt thereof.

According to another aspect of the present invention, there is provideda process for preparing said derivative having a1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable saltthereof.

According to still another aspect of the present invention, there isprovided a pharmaceutical composition comprising said derivative havinga 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptablesalt thereof as an active ingredient.

According to still another aspect of the present invention, there isprovided a therapeutic method comprising administering said derivativehaving a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceuticallyacceptable salt thereof.

According to still another aspect of the present invention, there isprovided a use of said derivative having a 1,2,3,4-tetrahydronaphthalenemoiety or pharmaceutically acceptable salt thereof for the manufactureof a medicament for inhibiting glucosylceramide synthase.

Advantageous Effects

It has been found by the present invention that the derivative having a6,6-fused bicyclic moiety, i.e., a 1,2,3,4-tetrahydronaphthalene moiety,or pharmaceutically acceptable salt thereof has an excellent inhibitoryactivity against glucosylceramide synthase (GCS). Therefore, thecompound or pharmaceutically acceptable salt thereof according to thepresent invention can be usefully applied for preventing or treatingvarious diseases associated with GCS, such as Gaucher disease, Fabrydisease, Tay-Sachs disease, Parkinson's disease, etc.

BEST MODE FOR CARRYING OUT THE INVENTION

As used herein, the term “alkyl” refers to a straight or branchedaliphatic hydrocarbon radical. For example, the C₁˜C₆ alkyl means astraight or branched aliphatic hydrocarbon having 1 to 6 carbon atoms,such as methyl, ethyl, propyl, n-butyl, n-pentyl, n-hexyl, isopropyl,isobutyl, sec-butyl, tert-butyl, neopentyl, and isopentyl.

The term “hydroxy” refers to the ‘—OH’ group. The term “alkoxy” refersto a radical formed by substituting the hydrogen atom in the hydroxylgroup with an alkyl. For example, the C₁˜C₆ alkoxy includes methoxy,ethoxy, propoxy, n-butoxy, n-pentyloxy, isopropoxy, sec-butoxy,tert-butoxy, neopentyloxy, and isopentyloxy.

The term “halogen” refers to the fluoro, bromo, chloro, or iodo group.

The term “cycloalkyl” refers to a saturated aliphatic 3- to 10-memberedring, preferably 3- to 7-membered ring, unless otherwise defined.Typical cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, and the like, but are not limited thereto.

The term “aryl” refers to an organic radical derived from an aromatichydrocarbon, through removing one hydrogen atom therefrom, includingmono or poly-fused ring systems such as 5- to 14-membered substituted orunsubstituted rings and a form in which a plurality of aryls areconnected by a single bond. The “aryl” includes, for example, phenyl,naphthyl, biphenyl, terphenyl, anthryl, indenyl, fluorenyl, phenanthryl,triphenylenyl, pyrenyl, perylenyl, chrysenyl, naphthacenyl,fluoranthenyl, and the like, but are not limited thereto.

The term “heteroaryl” refers to a 5- to 12-membered aromatic radicalhaving one to three heteroatoms selected from the group consisting ofnitrogen (N) atom, oxygen (O) atom, and sulfur (S) atom, including a 5-or 6-membered monocyclic heteroaryl radical and a bicyclic heteroarylradical formed by fusing the 5- or 6-membered monocyclic heteroarylradical with a benzene or pyridine ring. And, the term “heterocycle”refers to a 3- to 12-membered mono- or poly-cyclic ring having one ormore, preferably one to four, same or different heteroatoms selectedfrom oxygen (O) atom, nitrogen (N) atom, and sulfur (S) atom, but notcontaining an aromatic ring. Non-limiting examples of heteroaryl orheterocyclic rings include oxetane, pyrrolidine, pyrrole,tetrahydrofuran, furan, tetrahydrothiophene, thiophene, imidazolidine,imidazole, pyrazolidine, pyrazole, pyrrolizine, oxazolidine, oxazole,isoxazolidine, isoxazole, thiazolidine, thiazole, isothiazolidine,isothiazole, dioxolane, dithiolane, oxadiazole, thiadiazole, dithiazole,tetrazole, oxatetrazole, thiatetrazole, piperidine, pyridine,pyrimidine, tetrahydropyran, pyran, thiane, thiopyran, piperazine,diazine, morpholine, oxazine, dioxane, indole, indoline, benzodioxole,benzothiophene, benzofuran, benzimidazole, bezoxazole, benzisoxazole,benzothiazole, benzothiadiazole, benzotriazole, quinoline, isoquinoline,purine, furopyridine, mono- or di-azabicycles (such as quinuclidine,diazabicycloheptane, monoazabicyclooctane, diazaspiroundecane, etc.),hexahydropyrrolopyrrole, pyrrolopyrrole, pyrrolopyridine,imidazopyridazine, dihydrobenzodioxine, dihydrobenzofuran, and the like,but are not limited thereto.

The term “amino” refers to the ‘—NH₂’ group. The term “alkylamino”refers to an amino group substituted with mono- or di-alkyl. Forexample, the C₁˜C₆ alkylamino group includes an amino group substitutedwith mono- or di-C₁˜C₆ alkyl group.

The term “alkylthio” refers to the ‘—SR’ group, in which R is an alkyl.The term “cyano” refers to the ‘—CN’.

The present invention provides a derivative having a 6,6-fused bicyclicmoiety, i.e., a 1,2,3,4-tetrahydronaphthalene moiety or pharmaceuticallyacceptable salt thereof, that is a compound of Formula 1 orpharmaceutically acceptable salt thereof:

wherein,

L is —O—, —CO—, —CR₁R₂—, or —NR₃—,

R₁ and R₂ are, independently each other, hydrogen; halogen; C₁˜C₆ alkyl;C₁˜C₆ alkyl having a nitrogen, oxygen, or sulfur atom; C₃˜C₁₀cycloalkyl; 3- to 12-membered heterocyclic; or C₁˜C₆ alkoxy,

R₃ is hydrogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl having a nitrogen, oxygen, orsulfur atom; C₃˜C₁₀ cycloalkyl; 3- to 12-membered heterocyclic; or C₁˜C₆alkoxy,

X is hydrogen; halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl substituted with 1 to 3halogens; C₁˜C₆ alkyl having a nitrogen, oxygen, or sulfur atom; C₁˜C₆alkoxy; or C₁˜C₆ alkoxy substituted with 1 to 3 halogens,

Y, Q and Z are, independently each other, —CR₄R₅—,

R₄ and R₅ are, independently each other, hydrogen; halogen; C₁˜C₆ alkyl;C₁˜C₆ alkyl having a nitrogen, oxygen, or sulfur atom; C₃˜C₁₀cycloalkyl; 3- to 12-membered heterocyclic; or C₁˜C₆ alkoxy; or R₄ andR₅ form C₃˜C₁₀ cycloalkyl together with the carbon atom of Y, Q or Z towhich they are attached,

W is a bond, —CH₂—, —O—, —NH—, —CH₂CH₂—, —CH═CH—, or —C≡C—,

A ring is 6- to 12-membered aryl; 5- to 12-membered heteroaryl; C₃˜C₁₀cycloalkyl; or 3- to 12-membered heterocyclic, and

X₁, X₂, X₃, and X₄ are, independently each other, hydrogen; cyano;halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl substituted with 1 to 3 halogens;C₃˜C₁₀ cycloalkyl; 3- to 12-membered heterocyclic; C₁˜C₆ alkoxy; C₁˜C₆alkoxy-C₁˜C₆ alkoxy; C₁˜C₆ alkoxy substituted with 1 to 3 halogens;C₁˜C₆ alkylthio; morpholinyl; amino; mono- or di-C₁˜C₆ alkylamino; C₁˜C₆alkylcarbonyl; hydroxy; or nitro.

In the compound of Formula 1 or pharmaceutically acceptable salt thereofaccording to the present invention, L may be —O—.

In the compound of Formula 1 or pharmaceutically acceptable salt thereofaccording to the present invention, X may be hydrogen; halogen; or C₁˜C₆alkoxy.

In the compound of Formula 1 or pharmaceutically acceptable salt thereofaccording to the present invention, R₄ and R₅ may be, independently eachother, hydrogen or C₁˜C₆ alkyl; or may form C₃˜C₁₀ cycloalkyl togetherwith the carbon atom of Y, Q or Z to which they are attached. In anembodiment, Y may be —CH₂—. In another embodiment, Q may be —CH₂—. Instill another embodiment, Y may be —CH₂—; Q may be —CH₂—; and Z may be—CR₄R₅—; and R₄ and R₅ may be, independently each other, hydrogen orC₁˜C₆ alkyl or may form be C₃˜C₁₀ cycloalkyl together with the carbonatom of Z.

In the compound of Formula 1 or pharmaceutically acceptable salt thereofaccording to the present invention, W may be a bond (i.e., the A ring isdirectly bound to the 1,2,3,4-tetrahydronaphthalene moiety).

In the compound of Formula 1 or pharmaceutically acceptable salt thereofaccording to the present invention, the A ring may be phenyl,benzodioxolyl, 2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl,pyridinyl, pyrrolo[2.3-b]pyridinyl, pyrimidinyl, or thiophenyl.

In the compound of Formula 1 or pharmaceutically acceptable salt thereofaccording to the present invention, X₁, X₂, X₃, and X₄ may be,independently each other, hydrogen; cyano; halogen; C₁˜C₆ alkyl; C₁˜C₆alkyl substituted with 1 to 3 halogens; C₃˜C₁₀ cycloalkyl; C₁˜C₆ alkoxy;C₁˜C₆ alkoxy-C₁˜C₆ alkoxy; C₁˜C₆ alkoxy substituted with 1 to 3halogens; morpholinyl; mono- or di-C₁˜C₆ alkylamino; or C₁˜C₆alkylcarbonyl.

In a preferred embodiment of the present invention,

L is —O—,

X is hydrogen; halogen; or C₁˜C₆ alkoxy,

R₄ and R₅ are, independently each other, hydrogen or C₁˜C₆ alkyl; or R₄and R₅ form C₃˜C₁₀ cycloalkyl together with the carbon atom of Y, Q or Zto which they are attached,

W is a bond,

A ring is phenyl, benzodioxolyl, 2,3-dihydrobenzodioxinyl,2,3-dihydrobenzofuranyl, pyridinyl, pyrrolo[2.3-b]pyridinyl,pyrimidinyl, or thiophenyl, and

X₁, X₂, X₃, and X₄ are, independently each other, hydrogen; cyano;halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl substituted with 1 to 3 halogens;C₃˜C₁₀ cycloalkyl; C₁˜C₆ alkoxy; C₁˜C₆ alkoxy-C₁˜C₆ alkoxy; C₁˜C₆ alkoxysubstituted with 1 to 3 halogens; morpholinyl; mono- or di-C₁˜C₆alkylamino; or C₁˜C₆ alkylcarbonyl.

In said embodiment, Y may be —CH₂—.

In said embodiment, Q may be —CH₂—.

In said embodiment, Y may be —CH₂—; Q may be —CH₂—; and Z may be—CR₄R₅—; and R₄ and R₅ may be, independently each other, hydrogen orC₁˜C₆ alkyl or may form be C₃˜C₁₀ cycloalkyl together with the carbonatom of Z.

In the compound of Formula 1 or pharmaceutically acceptable salt,preferable compounds include a compound, including a pharmaceuticallyacceptable salt thereof, selected from the group consisting of:

-   (S)-quinuclidin-3-yl    (6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(difluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,3-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-butylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-isobutylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-cyclopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,3-dihydrobenzofuran-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-morpholinophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-methoxypyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-(chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(o-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-propoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(benzo[d]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(m-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,4-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-methoxypyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-fluoropyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(tert-butyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2,6-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate-   (S)-quinuclidin-3-yl    (6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-acetylthiophen-3-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (2,2-dimethyl-7-(2-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(4-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(4-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(4-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(4-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(3-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(3-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(3-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(3-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(2-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(2-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(2-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(2-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(p-tolyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(4-(difluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7′-(4-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(2-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(2-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(2-chloro-4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-chloro-3-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-fluoro-4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-ethylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate    (S)-quinuclidin-3-yl    (6′-(3-(tert-butyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-isopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-(difluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-(dimethylamino)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-isopropoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(2,3-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(2,4-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(2,5-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (6′-(2,6-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3,4-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3,5-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-ethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(3-ethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-isopropoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-propoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-ethylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-propylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-isopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-isobutylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-(tert-butyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (6′-(4-cyclopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-fluoro-6-(3-fluoro-4-methoxyphenyll)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;-   (S)-quinuclidin-3-yl    (6-(2-(tert-butoxy)pyridin-4-yl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;    and-   (S)-quinuclidin-3-yl    (6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.

The compound of Formula 1 or pharmaceutically acceptable salt thereofmay be in the form of cis- or trans-geometrical isomer. The compound ofFormula 1 or its pharmaceutically acceptable salt comprises both cis-and trans-geometrical isomers, unless otherwise indicated. The compoundof Formula 1 or pharmaceutically acceptable salt thereof may also havesubstituents containing asymmetric atom and therefore be in the form ofracemic mixture (RS) or in the form of an optical isomer, such as (R) or(S) isomer. The compound of Formula 1 or pharmaceutically acceptablesalt thereof comprises both the racemic mixture (RS) and each opticalisomer such as (R) or (S) isomer, unless otherwise indicated. Inaddition, the compound of Formula 1 or pharmaceutically acceptable saltthereof may have two or more chiral centers and therefore be in the formof one or more diastereomers or in the form of the mixture thereof. Thecompound of Formula 1 or pharmaceutically acceptable salt thereofcomprises both each diastereomer and the mixture thereof, unlessotherwise indicated.

The compound of Formula 1 of the present invention may be in apharmaceutically acceptable salt form. The salt may be a conventionalacid addition salt form, which includes e.g., salts derived from aninorganic acid such as hydrochloric acid, sulfuric acid, nitric acid,phosphoric acid, perchloric acid, or hydrobromic acid; and salts derivedfrom an organic acid such as formic acid, acetic acid, propionic acid,oxalic acid, succinic acid, benzoic acid, citric acid, maleic acid,malonic acid, malic acid, tartaric acid, gluconic acid, lactic acid,gentisic acid, fumaric acid, lactobionic acid, salicylic acid, phthalicacid, embonic acid, aspartic acid, glutamic acid, or acetylsalicylicacid. And, the salt also includes, e.g., salts derived from an aminoacid such as glycine, alanine, valine, isoleucine, serine, cysteine,cystine, aspartic acid, glutamine, lysine, arginine, tyrosine, orproline. In addition, the salt includes, e.g., salts derived from asulfonic acid such as methanesulfonic acid, ethanesulfonic acid,benzenesulfonic acid, or toluenesulfonic acid.

The compound of Formula 1 or pharmaceutically acceptable salt thereofaccording the present invention may be prepared according to variousmethods.

For example, the compound of Formula 1a or pharmaceutically acceptablesalt thereof according the present invention may be prepared by aprocess which comprises reacting a compound of Formula 2 or salt thereofwith ethyl chloroformate to obtain a compound of Formula 3; coupling thecompound of Formula 3 with a compound of Formula 4 to obtain a compoundof Formula 5; reacting the compound of Formula 5 with a A-W-boronic acidsubstituted with X₁, X₂, X₃, or X₄ to obtain a compound of Formula 1a;and optionally converting the compound of Formula 1a to apharmaceutically acceptable salt thereof, as shown in the followingReaction Scheme 1.

In the Reaction Scheme 1, X, Y, Q, Z, W, A ring, X₁, X₂, X₃, and X₄ arethe same as defined in the above.

The compound of Formula 2, which is commercially available or a knowncompound, may be synthesized according to literatures. The reactionbetween the compound of Formula 2 or salt thereof and ethylchloroformate may be carried out in the presence of an organic base suchas triethylamine, N,N-diisopropylethylamine, etc. or an inorganic basesuch as potassium carbonate, etc. The base may be used in an amountranging from 1 to 1.5 equivalents based on 1 equivalent of the compoundof Formula 2 or in an amount ranging from 3 to 5 equivalents based on 1equivalent of the salt of the compound of Formula 2 (e.g.,hydrochloride). The reaction may be carried out in a solvent such asdichloromethane or tetrahydrofuran preferably at 0° C. to roomtemperature.

The coupling between the compound of Formula 3 and the compound ofFormula 4 (i.e., quinuclidinol) may be carried out through acondensation reaction including the removal of ethanol. The reaction maybe carried out preferably in the presence of a base such as sodiumhydride. In addition, the reaction may be carried out in a non-polarorganic solvent such as toluene at 120° C. to 140° C.

The reaction between the compound of Formula 5 and the A-W-boronic acidsubstituted with X₁, X₂, X₃, or X₄ may be carried out according to theSuzuki reaction. Said Suzuki reaction may be carried out using apalladium catalyst, such as tetrakis(triphenylphosphine)palladium(0)(Pd(PPh₃)₄), palladium(II) acetate (Pd(OAc)₂),[1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)(Pd(dppf)C₁₂), etc. In addition, said Suzuki reaction may be carried outin the presence of an inorganic base such as cesium carbonate (Cs₂CO₃),sodium carbonate (Na₂CO₃), potassium carbonate (K₂CO₃), potassiumphosphate (K₃PO₄), etc. Said Suzuki reaction may be carried out in anon-polar organic solvent such as toluene or a polar organic solventsuch as 1,4-dioxane, tetrahydrofuran, acetonitrile, 1,2-dimethoxyethane,or N,N-dimethylformamide, at 50° C. to 150° C., preferably 80° C. to120° C. Other reaction conditions including a reaction time may bedetermined according to known methods for the Suzuki reaction.

The conversion of the compound of Formula 1a to a pharmaceuticallyacceptable salt thereof may be carried out according to conventionalmethods. For example, a pharmaceutically acceptable salt of the compoundof Formula 1a may be prepared by dissolving the compound of Formula 1ain a water-miscible solvent such as methanol, ethanol, acetone or1,4-dioxane and then added a free acid or a free base thereto for thecrystallization thereof.

In addition, the compound of Formula 1a or pharmaceutically acceptablesalt thereof according the present invention may be prepared by aprocess which comprises reacting a compound of Formula 4 withbis(4-nitrophenyl) carbonate to obtain a compound of Formula 7; reactingthe compound of Formula 7 with a compound of Formula 2 to obtain acompound of Formula 5; reacting the compound of Formula 5 with aA-W-boronic acid substituted with X₁, X₂, X₃, or X₄ to obtain a compoundof Formula 1a; and optionally converting the compound of Formula 1a to apharmaceutically acceptable salt thereof, as shown in the followingReaction Scheme 2.

In the Reaction Scheme 2, X, Y, Q, Z, W, A ring, X₁, X₂, X₃, and X₄ arethe same as defined in the above.

The reaction between the compound of Formula 4 (i.e., quinuclidinol) andbis(4-nitrophenyl) carbonate may be carried out in a polar solvent suchas N,N-dimethylformamide preferably at 0° C. to 25° C. The compound ofFormula 7 may be also prepared by reacting the compound of Formula 4with 4-nitrophenyl chloroformate, in the presence of a base such astriethylamine, in a solvent such as dichloromethane, acetonitrile, etc.

The reaction between the compound of Formula 7 and the compound ofFormula 2 may be carried out in a solvent such as N,N-dimethylformamide,tetrahydrofuran or acetonitrile, in the presence of a base such asN,N-diisopropylethylamine or triethylamine, at 0° C. to 25° C.

The reaction between the compound of Formula 5 and the A-W-boronic acidsubstituted with X₁, X₂, X₃, or X₄ may be carried out according to theSuzuki reaction, as described in the above. In addition, the conversionof the compound of Formula 1a to a pharmaceutically acceptable saltthereof may be carried out according to conventional methods, asdescribed in the above.

The compound having a 1,2,3,4-tetrahydronaphthalene moiety according tothe present invention, i.e., the compound of Formula 1 orpharmaceutically acceptable salt thereof has an excellent inhibitoryactivity against glucosylceramide synthase (GCS), and therefore can beusefully applied for preventing or treating treating various diseasesassociated with GCS.

Therefore, the present invention includes, within its scope, apharmaceutical composition for inhibiting glucosylceramide synthase(GCS), comprising a therapeutically effective amount of the compound ofFormula 1 or pharmaceutically acceptable salt thereof as an activeingredient. In an embodiment, the present invention provides apharmaceutical composition for preventing or treating the diseasesassociated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachsdisease, Parkinson's disease, etc., comprising a therapeuticallyeffective amount of the compound of Formula 1 or pharmaceuticallyacceptable salt thereof as an active ingredient.

The pharmaceutical composition of the present invention may comprise apharmaceutically acceptable carrier, such as diluents, disintegrants,sweeteners, lubricants, or flavoring agents. The pharmaceuticalcomposition may be formulated to an oral dosage form such as tablets,capsules, powders, granules, suspensions, emulsions, or syrups; or aparenteral dosage form such as solutions for external use, suspensionsfor external use, emulsions for external use, gels (e.g., ointment),inhalations, nebulizations, injections. The dosage form may be variousforms, e.g., dosage forms for single administration or for multipleadministrations.

The pharmaceutical composition of the present invention may comprise,for example, a diluent (e.g., lactose, corn starch, etc.); a lubricant(e.g., magnesium stearate); an emulsifying agent; a suspending agent; astabilizer; and/or an isotonic agent. If necessary, the compositionfurther comprises sweeteners and/or flavoring agents.

The composition of the present invention may be administered orally orparenterally, including inhalant, intravenous, intraperitoneal,subcutaneous, rectal and topical routes of administration. Therefore,the composition of the present invention may be formulated into variousforms such as tablets, capsules, aqueous solutions or suspensions. Inthe case of tablets for oral administration, carriers such as lactose,corn starch, and lubricating agents, e.g. magnesium stearate, areconventionally used. In the case of capsules for oral administration,lactose and/or dried corn starch can be used as a diluent. When anaqueous suspension is required for oral administration, the activeingredient may be combined with emulsifying and/or suspending agents. Ifdesired, certain sweetening and/or flavoring agents may be used. Forintramuscular, intraperitoneal, subcutaneous and intravenousadministration, sterile solutions of the active ingredient are usuallyprepared, and the pH of the solutions should be suitably adjusted andbuffered. For intravenous administration, the total concentration ofsolutes should be controlled in order to render the preparationisotonic. The composition of the present invention may be in the form ofan aqueous solution containing pharmaceutically acceptable carriers,e.g., saline having a pH level of 7.4. The solutions may be introducedinto a patient's intramuscular blood-stream by local bolus injection.

The compound of Formula 1 or pharmaceutically acceptable salt thereofmay be administered in a therapeutically effective amount ranging fromabout 0.0001 mg/kg to about 100 mg/kg per day to a subject patient. Ofcourse, the dosage may be changed according to the patient's age,weight, susceptibility, symptom, or activity of the compound.

The present invention includes, within its scope, a method forinhibiting glucosylceramide synthase (GCS) in a mammal, comprisingadministering a therapeutically effective amount of the compound ofFormula 1 or pharmaceutically acceptable salt thereof to the mammal inneed thereof. In an embodiment, the present invention provides a methodfor treating the diseases associated with GCS, such as Gaucher disease,Fabry disease, Tay-Sachs disease, Parkinson's disease, etc., comprisingadministering a therapeutically effective amount of the compound ofFormula 1 or pharmaceutically acceptable salt thereof to the mammal inneed thereof.

The present invention also provides a use of the compound of Formula 1or pharmaceutically acceptable salt thereof for the manufacture of amedicament for inhibiting glucosylceramide synthase (GCS) in a mammal.In an embodiment, the present invention provides a use of the compoundof Formula 1 or pharmaceutically acceptable salt thereof for themanufacture of a medicament for preventing or treating the diseasesassociated with GCS, such as Gaucher disease, Fabry disease, Tay-Sachsdisease, Parkinson's disease, etc.

The following examples and experimental examples are provided forillustration purposes only, and are not intended to limit the scope ofthe invention.

In the following examples, brine refers to a saturated aqueous sodiumchloride solution. Unless otherwise indicated, all temperatures are indegrees Celsius (° C.). All reactions were carried out at roomtemperature unless otherwise indicated.

The analyses of the compounds prepared in the following Preparations andExamples were carried out as follows: Nuclear magnetic resonance (NMR)spectrum analysis was carried out using Bruker 400 MHz spectrometer andchemical shifts thereof were analyzed in ppm. Column chromatography wascarried out on silica gel (Merck, 70-230 mesh). Each starting materialis a known compound which was synthesized according to literatures orpurchased commercially. All reactions and chromatographic fractions wereanalyzed by thin layer chromatography (TLC) on a 250 nm silica gel plateand visualized with ultraviolet or iodine (12) staining.

Preparation 1. (S)-quinuclidin-3-yl(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate Step 1. ethyl(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

6-Bromo-1,2,3,4-tetrahydronaphthalen-1-amine (20 g, 82.6 mmol) wasdissolved in dichloromethane (250 mL) and then triethylamine (12.7 ml,90.9 mmol) and ethyl chloroformate (8.7 ml, 90.9 mmol) were slowly addedthereto. The reaction mixture was stirred at room temperature for 4hours. Water was added to the reaction mixture, which was then extractedwith dichloromethane. The organic layer was dried over anhydrousmagnesium sulfate and then filtered and concentrated under reducedpressure. The resulting residue was purified by column chromatography(n-hexane/ethyl acetate=1/1, v/v) to give the titled compound as a whitesolid. (20.7 g, Yield: 83%)

¹H-NMR (400 MHz, CDCl₃) δ 7.31˜7.21 (m, 3H), 4.85 (s, 1H), 4.18 (m, 2H),2.76 (m, 2H), 2.06 (m, 1H), 1.83 (m, 3H), 1.28 (t, 3H)

Step 2. (S)-quinuclidin-3-yl(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

(S)-(+)-3-Quinuclidinol (25.6 g, 201.2 mmol) was dissolved in toluene(200 ml) and then sodium hydride (1.6 g, 67.1 mmol) was added thereto at0° C. The reaction mixture was stirred for 15 minutes and then ethyl(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate (20 g, 67.1 mmol)prepared in Step 1 was added thereto. The reaction mixture was refluxedunder stirring at 140° C. for 21 hours and then cooled to roomtemperature. Brine was added to the reaction mixture, which was thenextracted with ethyl acetate. The organic layer was washed with brinetwo times, dried over anhydrous magnesium sulfate, and then concentratedunder reduced pressure. The resulting residue was purified by columnchromatography (ethyl acetate/(methanol/ammonia water=1/1)=9/1, v/v) togive the titled compound as a white solid. (17 g, Yield: 66%)

¹H-NMR (400 MHz, CDCl₃) δ 7.31˜7.19 (m, 3H), 5.08 (m, 1H), 4.85 (m, 1H),4.77 (br, 1H), 3.24 (m, 1H), 2.84 (m, 2H), 2.74 (m, 4H), 2.10˜2.05 (m,3H), 1.83 (m, 4H), 1.69 (m, 1H), 1.58 (m, 1H), 1.38 (m, 1H)

Preparation 2. (S)-quinuclidin-3-yl(7-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Preparation 1, using 7-bromo-1,2,3,4-tetrahydronaphthalen-1-amineas a starting material.

¹H-NMR (400 MHz, CDCl₃) δ 7.39 (d, 1H), 7.28 (d, 1H), 7.02 (d, 1H), 4.76(s, 2H), 3.26 (q, 1H), 2.87˜2.71 (m, 7H), 2.11˜1.88 (m, 4H), 1.85˜1.72(m, 3H), 1.70˜1.61 (bs, 1H), 1.56˜1.46 (m, 1H)

Preparation 3. (S)-quinuclidin-3-yl(6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateStep 1. 6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one

6-Bromo-1,2,3,4-tetrahydronaphthalen-1-one (20 g, 88.9 mmol) wasdissolved in tetrahydrofuran (70 ml) and then 60% sodium hydride (17.8g, 444.3 mmol) was added thereto at 0° C. The reaction mixture wasstirred for 15 minutes and then iodomethane (22.1 ml, 355.4 mmol) wasslowly added thereto at the same temperature. The reaction mixture wasstirred at room temperature overnight. Water was added to the reactionmixture, which was then extracted with ethyl acetate. The organic layerwas dried over anhydrous magnesium sulfate and then filtered andconcentrated under reduced pressure. The resulting residue was purifiedby column chromatography (n-hexane/ethyl acetate=10/1, v/v) to give thetitled compound as a white solid. (20 g, Yield: 90%)

¹H-NMR (400 MHz, CDCl₃) δ 8.03 (d, 1H), 7.74 (d, 1H), 7.21 (t, 1H), 3.00(m, 2H), 2.01 (m, 2H), 1.22 (s, 6H)

Step 2. 6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-aminehydrochloride

6-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one (20 g, 79.0mmol) prepared in Step 1 was dissolved in methanol (300 ml) and thenammonium acetate (121.8 g, 1580.1 mmol) and sodium cyanoborohydride(24.8 g, 395.0 mmol) were added thereto. The reaction mixture wasstirred at room temperature for 4 hours and then refluxed under stirringat 80° C. for 12 hours. The reaction mixture was cooled to roomtemperature, basified to pH>12 with a 1N sodium hydroxide solution, andthen extracted with dichloromethane. The organic layer was dried overanhydrous magnesium sulfate and then filtered and concentrated underreduced pressure. Ethyl acetate was added to the resulting residue andthen a hydrochloric acid solution (4M) in 1,4-dioxane was added thereto.The mixture was stirred at room temperature for 1 hour. The resultingsolid was filtered under reduced pressure, washed with ethyl acetate,and then dried to give the titled compound as a white solid. (12 g,Yield: 52%)

¹H-NMR (400 MHz, CD₃OD) δ 7.68 (d, 1H), 7.41 (d, 1H), 7.25 (t, 1H), 4.13(s, 1H), 2.96 (m, 1H), 2.75 (m, 1H), 1.88 (m, 1H), 1.75 (m, 1H), 1.20(s, 3H), 1.03 (s, 3H)

Step 3. (S)-quinuclidin-3-yl(6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

A solution of (S)-(+)-3-quinuclidinol (6.3 g, 49.5 mmo) andbis(4-nitrophenyl) carbonate (15.1 g, 49.5 mmol) inN,N-dimethylformamide (80 mL) was stirred at room temperature for 8hours. {{99.Solvent volume:row 1}}_XXXXX_

0

6-Bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride(20 g, 41.3 mmol) prepared in Step 2 and {{99.Reactant volume orquant:row 2}}_XXXXX_diisopropylethylamine (21.6 mL, 123.9 mmol) wereadded to the solution, which was then stirred at room temperatureovernight. The reaction mixture was extracted with diisopropyl ether(100 ml×2). The aqueous layer was basified to pH 12 with ammonia andthen extracted with ethyl acetate. The organic layer was washed withwater, dried over anhydrous magnesium sulfate, and then filtered andconcentrated under reduced pressure. The resulting residue was purifiedby column chromatography (ethyl acetate/(methanol/ammoniawater=1/1)=9/1, v/v) to give the titled compound as a white solid. (6 g,Yield: 36%)

¹H-NMR (400 MHz, CDCl₃) δ 7.25 (m, 2H), 7.12 (m, 1H), 5.09 (m, 1H), 4.95(m, 1H), 4.53 (m, 1H), 3.20 (m, 1H), 2.84˜2.65 (m, 7H), 1.95 (m, 1H),1.81 (m, 2H), 1.66 (br, 1H), 1.53 (br, 1H), 1.38 (br, 1H), 0.99 (m, 3H),0.88 (m, 3H)

Preparation 4. (S)-quinuclidin-3-yl(7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateStep 1. 7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one

The titled compound was prepared in accordance with the same proceduresas in Step 1 of Preparation 3, using7-bromo-3,4-dihydronaphthalen-1(2H)-one as a starting material.

¹H-NMR (400 MHz, CDCl₃) δ 8.16 (s, 1H), 7.57 (d, 1H), 7.12 (d, 1H), 2.94(m, 2H), 1.99 (m, 2H), 1.27 (s, 6H)

Step 2. (7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-aminehydrochloride

The titled compound was prepared in accordance with the same proceduresas in Step 2 of Preparation 3, using7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1(2H)-one prepared inStep 1.

¹H-NMR (400 MHz, MeOD) δ 7.60 (s, 1H), 7.51 (d, 1H), 7.20 (d, 1H), 4.09(s, 1H), 3.88 (m, 2H), 1.87 (m, 1H), 1.70 (m, 1H), 1.16 (s, 3H), 1.05(s, 3H)

Step 3. ethyl(7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Step 1 of Preparation 1, using7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine hydrochlorideprepared in Step 2. The product was used in subsequent reaction withoutfurther purification.

Step 4. (S)-quinuclidin-3-yl(7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Step 2 of Preparation 1, using ethyl(7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateprepared in Step 3.

¹H-NMR (400 MHz, CDCl₃) δ 7.40 (m, 1H), 7.25 (m, 1H), 6.95 (d, 1H), 5.09(m, 1H), 4.78 (m, 1H), 4.59 (m, 1H), 3.22 (m, 1H), 2.86˜2.68 (m, 7H),1.98 (m, 1H), 1.82 (m, 2H), 1.66 (m, 1H), 1.55 (m, 1H), 1.38 (m, 1H),1.00 (m, 3H), 0.88 (m, 3H)

Preparation 5. (S)-quinuclidin-3-yl(6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamateStep 1. (2-chloroethyl)dimethylsulfonium iodide

A solution of 2-chloroethyl methyl sulfide (10 g, 90.4 mmol) iniodomethane (50 ml) was stirred at room temperature for 2 days. Theresulting solid was filtered under reduced pressure, washed withacetone, and then dried to give the titled compound. (16 g, Yield: 70%)The product was used in subsequent reaction without furtherpurification.

Step 2.6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-one

6-Bromo-3,4-hydronaphthalen-1(2H)-one (1.03 g, 4.58 mmol) was dissolvedin tert-butanol (10 mL) and then sodium iodide (0.131 g, 0.872 mmol) and60% sodium hydride (0.349 g, 8.72 mmol) were slowly added thereto. Thereaction mixture was stirred at room temperature for 20 minutes.(2-Chloroethyl)dimethylsulfonium iodide (1.10 g, 4.36 mmol) prepared inStep 1 was slowly added over 1 hour to the reaction mixture, which wasthen stirred at room temperature overnight. The reaction was quenched byadding water (15 ml) to the reaction mixture, which was then extractedwith ethyl acetate. The organic layer was dried over anhydrous magnesiumsulfate and then filtered and concentrated under reduced pressure. Theresulting residue was purified by column chromatography (n-hexane/ethylacetate=10/1, v/v) to give the titled compound as a white solid. (789mg, Yield: 78%)

¹H-NMR (400 MHz, CDCl₃) δ 7.99 (d, 1H), 7.73 (d, 1H), 7.19 (t, 1H), 3.08(m, 2H), 1.99 (m, 2H), 1.40 (d, 2H), 0.86 (d, 2H)

Step 3.6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-aminehydrochloride

The titled compound was prepared in accordance with the same proceduresas in Step 2 of Preparation 3, using6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-oneprepared in Step 2.

¹H-NMR (400 MHz, MeOD) δ 7.67 (d, 1H), 7.37 (d, 1H), 7.23 (t, 1H), 3.68(s, 1H), 3.09 (m, 1H), 2.82 (m, 1H), 2.39 (m, 1H), 1.26 (m, 1H), 0.93(m, 1H), 0.79 (m, 1H), 0.69 (m, 1H), 0.55 (m, 1H)

Step 4. ethyl(6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Step 1 of Preparation 1, using6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-aminehydrochloride prepared in Step 3. The product was used in subsequentreaction without further purification.

¹H-NMR (400 MHz, CDCl₃) δ 7.48 (d, 1H), 7.30 (m, 1H), 7.06 (t, 1H), 4.98(br, 1H), 4.27 (d, 1H), 4.15 (m, 2H), 2.95 (m, 1H), 2.74 (m, 1H), 2.03(m, 1H), 1.31 (m, 1H), 1.27 (m, 3H), 0.85 (m, 1H), 0.50 (m, 1H), 0.45(s, 2H)

Step 5. (S)-quinuclidin-3-yl(6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Step 2 of Preparation 1, using ethyl(6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamateprepared in Step 4.

¹H-NMR (400 MHz, CDCl₃) δ 7.47 (d, 2H), 7.27 (m, 1H), 7.04 (m, 1H), 5.30(m, 1H), 4.78˜4.76 (m, 2H), 4.23 (d, 1H), 3.23 (m, 1H), 2.86˜2.67 (m,7H), 2.42 (br, 1H), 1.98 (m, 1H), 1.83 (m, 1H), 1.67 (m, 1H), 1.55 (m,1H), 1.37 (m, 1H), 0.85 (m, 1H), 0.47˜0.44 (m, 2H)

Preparation 6. (S)-quinuclidin-3-yl(7′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Preparation 5, using 7-bromo-3,4-hydronaphthalen-1(2H)-one as astarting material.

¹H-NMR (400 MHz, CDCl₃) δ 7.41 (s, 1H), 7.30 (m, 1H), 6.99 (d, 1H), 5.42(br, 1H), 4.77 (m, 2H), 4.26 (m, 1H), 3.22 (m, 1H), 2.85˜2.67 (m, 7H),2.10 (br, 1H), 1.98 (m, 1H), 1.83 (br, 1H), 1.67 (br, 1H), 1.55 (br,1H), 1.39 (br, 1H), 0.85 (m, 1H), 0.51 (m, 1H), 0.49 (m, 2H)

Preparation 7. (S)-quinuclidin-3-yl(6-bromo-7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Preparation 3, using6-bromo-7-fluoro-3,4-hydronaphthalen-1(2H)-one as a starting material.

¹H-NMR (400 MHz, CDCl₃) δ 7.29 (m, 2H), 7.04 (m, 1H), 4.78 (m, 2H), 4.56(d, 1H), 3.25 (m, 1H), 2.93˜2.74 (m, 7H), 2.09 (br, 1H), 1.82 (br, 1H),1.71 (br, 3H), 1.59 (br, 1H), 1.42 (br, 1H), 1.03 (d, 3H), 0.91 (d, 3H)

Preparation 8. (S)-quinuclidin-3-yl(6-bromo-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

The titled compound was prepared in accordance with the same proceduresas in Preparation 3, using6-bromo-7-methoxy-3,4-hydronaphthalen-1(2H)-one as a starting material.

¹H-NMR (400 MHz, CDCl₃) δ 7.27 (m, 2H), 6.79 (m, 1H), 4.77 (m, 2H), 4.55(d, 1H), 3.84 (d, 3H), 3.25 (m, 1H), 2.93˜2.74 (m, 7H), 2.09 (br, 1H),1.89 (br, 1H), 1.71 (br, 3H), 1.56 (br, 1H), 1.41 (br, 1H), 1.03 (d,3H), 0.95 (d, 3H)

Example 1. (S)-quinuclidin-3-yl(6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

To a mixture of(S)-quinuclidin-3-yl-(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate(30 mg, 0.079 mmol) prepared in Preparation 1, 4-fluorophenylboronicacid (16.6 mg, 0.12 mmol), potassium phosphate (50.4 mg, 0.23 mmol), andtetrakis(triphenylphosphine)palladium(0) (9.1 mg, 10 mol %), were slowlyadded 1,4-dioxane (1 ml) and water (0.5 ml). The reaction mixture wasrefluxed under stirring at 120° C. overnight and then cooled to roomtemperature. Water was added to the reaction mixture, which was thenextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate and then filtered and concentrated under reducedpressure. The resulting residue in the yellow oil form was purified bysilica gel column chromatography (ethyl acetate/(methanol/ammoniawater=1/1)=9/1, v/v) to give the titled compound as a white solid. (20mg, Yield: 65%)

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (m, 2H), 7.39 (m, 2H), 7.26 (m, 1H), 7.13(m, 2H), 5.02 (m, 2H), 4.80 (m, 1H), 3.27 (m, 1H), 2.87˜2.77 (m, 7H),2.08 (m, 2H), 1.89 (m, 4H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H)

Examples 2 to 54

The titled compounds of Examples 2 to 54 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(6-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared inPreparation 1; and the corresponding substituted-boronic acids,respectively.

Example 2. (S)-quinuclidin-3-yl(6-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (m, 2H), 7.42 (m, 3H), 7.29 (m, 2H), 5.00(m, 2H), 4.81 (br, 1H), 3.30 (m, 1H), 2.87˜2.77 (m, 7H), 2.06 (m, 2H),1.89 (m, 4H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

Example 3. (S)-quinuclidin-3-yl(6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (s, 3H), 7.45 (m, 2H), 7.35 (m, 1H), 7.28(d, 1H), 4.99 (m, 2H), 4.80 (br, 1H), 3.29 (m, 1H), 2.88˜2.77 (m, 7H),2.14 (m, 2H), 1.91 (m, 4H), 1.71 (br, 1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 4. (S)-quinuclidin-3-yl(6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.57 (d, 1H), 7.42 (m, 4H), 7.28 (m, 2H), 5.00(m, 2H), 4.80 (br, 1H), 3.28 (m, 1H), 2.86˜2.77 (m, 7H), 2.08 (m, 2H),1.90 (m, 4H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H)

Example 5. (S)-quinuclidin-3-yl(6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.46˜7.36 (m, 4H), 7.30˜7.28 (m, 2H), 7.04 (t,1H), 5.00 (m, 2H), 4.80 (m, 1H), 3.28 (m, 1H), 2.88˜2.77 (m, 7H), 2.13(m, 2H), 1.89 (m, 4H), 1.71 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H)

Example 6. (S)-quinuclidin-3-yl(6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.56 (s, 1H), 7.44 (m, 1H), 7.37 (m, 2H), 7.23(m, 2H), 5.00 (m, 2H), 4.80 (br, 1H), 3.28 (m, 1H), 2.88˜2.77 (m, 7H),2.09 (m, 2H), 1.90˜1.82 (m, 4H), 1.71 (br, 1H), 1.60 (m, 1H), 1.41 (m,1H)

Example 7. (S)-quinuclidin-3-yl(6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.81 (s, 1H), 7.76 (d, 1H), 7.62˜7.54 (m, 2H),7.44 (m, 2H), 7.34 (s, 1H), 5.06˜5.03 (m, 2H), 4.81 (br, 1H), 3.28 (m,1H), 2.88˜2.74 (m, 7H), 2.12 (m, 2H), 1.90 (m, 3H), 1.83 (br, 1H), 1.71(br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

Example 8. (S)-quinuclidin-3-yl(6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50˜7.41 (m, 5H), 7.31 (s, 1H), 7.22 (m, 1H),5.06˜5.04 (m, 2H), 4.80 (br, 1H), 3.27 (m, 1H), 2.87˜2.77 (m, 7H), 2.08(m, 2H), 1.90 (m, 3H), 1.82 (br, 1H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40(br, 1H)

Example 9. (S)-quinuclidin-3-yl(6-(2-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.44 (m, 3H), 7.34 (m, 2H), 7.23 (m, 1H), 7.18(m, 1H), 5.03 (m, 1H), 4.97 (br, 1H), 4.80 (br, 1H), 3.28 (m, 1H),2.86˜2.77 (m, 7H), 2.06 (m, 2H), 1.90 (m, 4H), 1.70 (br, 1H), 1.60 (br,1H), 1.40 (br, 1H)

Example 10. (S)-quinuclidin-3-yl(6-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.66 (m, 1H), 7.44 (m, 4H), 7.18(s, 1H), 5.08 (m, 1H), 4.98 (br, 1H), 4.81 (br, 1H), 3.28 (m, 1H),2.90˜2.78 (m, 7H), 2.13 (m, 1H), 1.90 (m, 5H), 1.70 (br, 1H), 1.60 (br,1H), 1.40 (br, 1H)

Example 11. (S)-quinuclidin-3-yl(6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.74 (m, 1H), 7.56 (m, 1H), 7.55 (, 1H), 7.47(br, 1H), 7.32 (m, 1H), 7.16 (br, 1H), 7.07 (s, 1H), 5.07 (m, 1H), 4.96(m, 1H), 4.80 (m, 1H), 3.29 (m, 1H), 2.88˜2.81 (m, 7H), 2.09 (m, 2H),1.90 (m, 4H), 1.71 (br, 1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 12. (S)-quinuclidin-3-yl(6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.41˜7.37 (m, 4H), 7.31 (m, 2H), 7.20 (s 1H),5.08 (m, 1H), 4.97 (br, 1H), 4.81 (m, 1H), 3.30 (m, 1H), 2.86˜2.78 (m,7H), 2.14 (m, 2H), 1.90 (m, 4H), 1.70 (br, 1H), 1.60 (br, 1H), 1.40 (br,1H)

Example 13. (S)-quinuclidin-3-yl(6-(4-(difluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.55 (d, 2H), 7.40 (m, 2H), 7.29 (s, 1H), 7.18(d, 2H), 6.74˜6.37 (t, 1H), 5.18 (m, 1H), 4.95 (m, 1H), 4.79 (m, 1H),3.27 (m, 1H), 2.86˜2.72 (m, 7H), 2.08 (m, 2H), 1.88 (m, 3H), 1.82 (br,1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.40 (br, 1H)

Example 14. (S)-quinuclidin-3-yl(6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.49 (d, 2H), 7.42 (d, 2H), 7.32 (s, 1H), 7.27(m, 3H), 4.99 (m, 2H), 4.79 (br, 1H), 3.30 (m, 1H), 2.87˜2.78 (m, 7H),2.41 (s, 3H), 2.08 (m, 2H), 1.89 (m, 3H), 1.82 (br, 1H), 1.70 (br, 1H),1.59 (br, 1H), 1.41 (br, 1H)

Example 15. (S)-quinuclidin-3-yl(6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43 (m, 1H), 7.37 (m, 2H), 7.26 (m, 2H), 7.21(m, 1H), 4.98 (m, 1H), 4.96 (m, 1H), 4.80 (br, 1H), 3.30 (m, 1H),2.87˜2.78 (m, 7H), 2.09 (m, 2H), 1.89 (m, 3H), 1.81 (m, 2H), 1.71 (br,1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 16. (S)-quinuclidin-3-yl(6-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (m, 1H), 7.37 (m, 1H), 7.12 (m, 2H), 7.00(m, 1H), 5.02 (m, 2H), 4.81 (m, 1H), 3.31 (m, 1H), 2.87˜2.78 (m, 7H),2.06 (m, 2H), 1.89 (m, 4H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

Example 17. (S)-quinuclidin-3-yl(6-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (m, 1H), 7.39 (m, 1H), 7.29 (m, 1H), 7.10(d, 2H), 6.79 (m, 1H), 5.00 (m, 1H), 4.96 (m, 1H), 4.81 (br, 1H), 3.30(m, 1H), 2.87˜2.77 (m, 7H), 2.13 (m, 2H), 1.89 (m, 4H), 1.71 (br, 1H),1.61 (br, 1H), 1.41 (br, 1H)

Example 18. (S)-quinuclidin-3-yl(6-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43 (m, 2H), 7.32 (m, 1H), 7.24 (s, 1H), 6.94(m, 2H), 5.00 (m, 1H), 4.96 (br, 1H), 4.79 (br, 1H), 3.30 (m, 1H),2.86˜2.77 (m, 7H), 2.14 (m, 2H), 1.89˜1.83 (m, 4H), 1.70 (br, 1H), 1.60(br, 1H), 1.41 (br, 1H)

Example 19. (S)-quinuclidin-3-yl(6-(2,3-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (t, 1H), 7.37 (br, 1H), 7.28 (m, 1H),7.15 (m, 3H), 5.01 (m, 1H), 4.97 (m, 1H), 4.81 (br, 1H), 3.30 (m, 1H),2.86˜2.75 (br, 7H), 2.13 (m, 2H), 1.90 (m, 2H), 1.82 (m, 2H), 1.71 (br,1H), 1.59 (br, 1H), 1.40 (br, 1H)

Example 20. (S)-quinuclidin-3-yl(6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (t, 1H), 7.32 (m, 1H), 7.24 (s, 1H), 7.14(m, 1H), 7.05 (m, 1H), 5.01 (m, 2H), 4.80 (br, 1H), 3.30 (m, 1H),2.87˜2.78 (m, 7H), 2.14 (m, 2H), 1.90 (m, 2H), 1.80 (m, 2H), 1.71 (br,1H), 1.60 (br, 1H), 1.41 (br, 1H)

Example 21. (S)-quinuclidin-3-yl(6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.46 (m, 1H), 7.31 (m, 1H), 7.25 (m, 2H), 7.02(t, 1H), 5.00 (m, 2H), 4.80 (br, 1H), 3.28 (m, 1H), 2.86˜2.73 (m, 7H),2.14 (m, 2H), 1.89 (m, 2H), 1.82 (m, 2H), 1.71 (br, 1H), 1.60 (br, 1H),1.41 (br, 1H)

Example 22. (S)-quinuclidin-3-yl(6-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.66 (m, 1H), 7.51˜7.49 (m, 2H), 7.41 (m, 3H),4.99 (m, 2H), 4.80 (br, 1H), 3.30 (m, 1H), 2.87˜2.78 (m, 7H), 2.13 (m,2H), 1.90 (m, 2H), 1.82 (m, 2H), 1.71 (br, 1H), 1.61 (br, 1H), 1.42 (br,1H)

Example 23. (S)-quinuclidin-3-yl(6-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42 (m, 2H), 7.32 (s, 1H), 7.26 (m, 2H), 7.15(s, 1H), 5.05 (m, 1H), 4.97 (m, 1H), 4.81 (br, 1H), 3.28 (m, 1H),2.88˜2.77 (m, 7H), 2.13 (m, 2H), 1.90˜1.87 (m, 4H), 1.70 (br, 1H), 1.60(br, 1H), 1.41 (br, 1H)

Example 24. (S)-quinuclidin-3-yl(6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.57 (m, 1H), 7.49 (m, 1H), 7.44 (s, 2H), 7.36(m, 1H), 7.34 (m, 1H), 5.00 (m, 2H), 4.81 (br, 1H), 3.28 (m, 1H),2.87˜2.78 (m, 7H), 2.13 (m, 2H), 1.90 (m, 2H), 1.84 (m, 2H), 1.71 (br,1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 25. (S)-quinuclidin-3-yl(6-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (d, 2H), 7.40 (m, 2H), 7.28 (m, 1H), 7.01(d, 2H), 5.02 (m, 1H), 4.95˜4.81 (m, 2H), 4.19 (d, 2H), 3.81 (d, 2H),3.79 (s, 3H), 3.30 (m, 1H), 2.90˜2.80 (m, 7H), 2.06 (m, 4H), 1.99 (m,2H), 1.73 (br, 1H), 1.63 (br, 1H), 1.44 (br, 1H)

Example 26. (S)-quinuclidin-3-yl(6-(4-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (m, 2H), 7.40 (m, 2H), 7.28 (m, 1H), 7.12(d, 2H), 5.23 (s, 2H), 5.07 (m, 1H), 4.94˜4.80 (m, 2H), 3.52 (s, 3H),3.29 (m, 1H), 2.86˜2.78 (m, 7H), 2.06 (m, 2H), 1.88 (m, 4H), 1.70 (br,1H), 1.60 (br, 1H), 1.40 (br, 1H)

Example 27. (S)-quinuclidin-3-yl(6-(3-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42 (m, 2H), 7.37 (m, 2H), 7.18 (m, 2H), 6.94(d, 1H), 5.02 (m, 1H), 4.95˜4.82 (m, 2H), 4.21 (d, 2H), 3.80 (d, 2H),3.80 (s, 3H), 3.31 (m, 1H), 2.91˜2.81 (m, 7H), 2.31 (br, 2H), 2.12 (m,2H), 1.89 (m, 2H), 1.73 (br, 1H), 1.62 (br, 1H), 1.44 (br, 1H)

Example 28. (S)-quinuclidin-3-yl(6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.41 (d, 2H), 7.36 (m, 2H), 7.25 (m, 2H), 7.05(d, 1H), 5.24 (s, 2H), 5.12 (m, 1H), 4.95˜4.80 (m, 2H), 3.52 (s, 3H),3.28 (m, 1H), 2.87˜2.75 (m, 7H), 2.50 (br, 1H), 2.06 (m, 2H), 1.88 (m,3H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

Example 29. (S)-quinuclidin-3-yl(6-(2-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43˜7.30 (m, 5H), 7.04˜6.99 (m, 2H), 5.10 (m,1H), 4.95˜4.80 (m, 2H), 4.13 (d, 2H), 3.71 (d, 2H), 3.41 (s, 3H), 3.28(m, 1H), 2.88˜2.79 (m, 7H), 2.39 (br, 1H), 2.06 (m, 2H), 1.88 (m, 3H),1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

Example 30. (S)-quinuclidin-3-yl(6-(2-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.38 (d, 2H), 7.29 (m, 2H), 7.24 (m, 2H), 7.11(t, 1H), 5.15 (s, 2H), 5.10 (m, 1H), 4.96˜4.79 (m, 2H), 3.45 (s, 3H),3.28 (m, 1H), 2.88˜2.77 (m, 7H), 2.46 (br, 1H), 2.06 (m, 2H), 1.89 (m,3H), 1.71 (br, 1H), 1.60 (br, 1H), 1.42 (br, 1H)

Example 31. (S)-quinuclidin-3-yl(6-(4-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.52 (m, 2H), 7.43 (m, 2H), 7.28 (d, 3H), 5.14(m, 1H), 4.98˜4.81 (m, 2H), 3.30 (m, 1H), 2.87 (m, 7H), 2.70 (q, 2H),2.10 (m, 2H), 1.89 (m, 4H), 1.71 (br, 1H), 1.61 (br, 1H), 1.42 (br, 1H),1.29 (t, 3H)

Example 32. (S)-quinuclidin-3-yl(6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (d, 1H), 7.43 (m, 2H), 7.27 (m, 3H), 5.09(m, 1H), 4.96˜4.80 (m, 2H), 3.30 (m, 1H), 2.87˜2.76 (m, 7H), 2.64 (t,2H), 2.10 (m, 2H), 1.89 (m, 3H), 1.74 (m, 3H), 1.61 (br, 1H), 1.42 (br,1H), 0.99 (t, 3H)

Example 33. (S)-quinuclidin-3-yl(6-(4-butylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (d, 2H), 7.42 (d, 2H), 7.27 (m, 3H), 5.11(m, 1H), 4.96˜4.81 (m, 2H), 3.32 (m, 1H), 2.87˜2.78 (m, 7H), 2.66 (t,2H), 2.10 (m, 2H), 1.89 (m, 3H), 1.72 (br, 1H), 1.67 (m, 3H), 1.43 (m,3H), 0.98 (t, 3H)

Example 34. (S)-quinuclidin-3-yl(6-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.52 (d, 2H), 7.42 (m, 2H), 7.32 (m, 3H), 5.05(m, 1H), 4.96˜4.81 (m, 2H), 3.30 (m, 1H), 2.97 (m, 1H), 2.87˜2.79 (m,7H), 2.26 (br, 1H), 2.07 (m, 2H), 1.89 (m, 3H), 1.72 (br, 1H), 1.61 (br,1H), 1.42 (br, 1H), 1.25 (d, 6H)

Example 35. (S)-quinuclidin-3-yl(6-(4-isobutylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (d, 1H), 7.43 (m, 3H), 7.33 (s, 1H), 7.23(d, 2H), 5.10 (m, 1H), 4.95˜4.81 (m, 2H), 3.30 (m, 1H), 2.87˜2.78 (m,7H), 2.52 (d, 2H), 2.08 (m, 2H), 1.89 (m, 4H), 1.70 (br, 1H), 1.60 (br,1H), 1.40 (br, 1H), 0.96 (d, 6H)

Example 36. (S)-quinuclidin-3-yl(6-(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (m, 1H), 7.51 (m, 3H), 7.46 (m, 2H), 7.33(s, 1H), 5.05 (m, 1H), 4.96˜4.81 (m, 2H), 3.30 (m, 1H), 2.88˜2.78 (m,7H), 2.31 (br, 1H), 2.06 (m, 2H), 1.88 (m, 3H), 1.72 (br, 1H), 1.61 (br,1H), 1.38 (br, 1H), 1.28 (s, 9H)

Example 37. (S)-quinuclidin-3-yl(6-(4-cyclopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.48˜7.41 (m, 4H), 7.31 (m, 1H), 7.15 (m, 2H),5.14 (m, 1H), 4.94˜4.80 (m, 2H), 3.28 (m, 1H), 2.86˜2.78 (m, 7H), 2.08(m, 2H), 1.88 (m, 4H), 1.71 (br, 1H), 1.61 (br, 1H), 1.41 (br, 1H), 1.01(m, 2H), 0.75 (m, 2H)

Example 38. (S)-quinuclidin-3-yl(6-(3-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43 (m, 4H), 7.33 (m, 2H), 7.21 (d, 1H), 5.10(m, 1H), 4.96˜4.80 (m, 2H), 3.30 (m, 1H), 2.87˜2.75 (m, 7H), 2.74 (q,2H), 2.09 (m, 2H), 1.89 (m, 4H), 1.71 (br, 1H), 1.0 (br, 1H), 1.42 (br,1H), 1.30 (t, 3H)

Example 39. (S)-quinuclidin-3-yl(6-(3-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.58 (s, 1H), 7.44 (s, 2H), 7.42 (m, 3H), 7.32(s, 1H), 5.03 (m, 1H), 4.97˜4.81 (m, 2H), 3.30 (m, 1H), 2.89˜2.80 (m,7H), 2.14 (m, 2H), 1.90 (m, 4H), 1.73 (br, 1H), 1.60 (br, 1H), 1.40 (br,1H), 1.39 (s, 9H) Example 40. (S)-quinuclidin-3-yl(6-(3-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.44˜7.33 (m, 6H), 7.24 (m, 1H), 5.11 (m, 1H),4.96˜4.80 (m, 2H), 3.30 (m, 1H), 3.02 (m, 1H), 2.88˜2.75 (m, 7H), 2.55(br, 1H), 2.14 (m, 2H), 1.89 (m, 3H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41(br, 1H), 1.28 (d, 6H)

Example 41. (S)-quinuclidin-3-yl(6-(2-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.40 (m, 1H), 7.32 (m, 3H), 7.23 (m, 1H), 7.18(m, 1H), 7.05 (s, 1H), 5.15 (m, 1H), 4.97˜4.81 (m, 2H), 3.28 (m, 1H),2.88˜2.77 (m, 7H), 2.62 (q, 2H), 2.46 (br, 1H), 2.06 (m, 2H), 1.89 (m,3H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H), 1.13 (t, 3H)

Example 42. (S)-quinuclidin-3-yl(6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (t, 1H), 7.36 (m, 1H), 7.25 (m, 3H), 7.12(d, 1H), 5.07 (m, 1H), 4.95˜4.80 (m, 2H), 3.29 (m, 1H), 2.87˜2.78 (m,7H), 2.43 (br, 1H), 2.13 (m, 2H), 1.89 (m, 3H), 1.71 (br, 1H), 1.60 (br,1H), 1.41 (br, 1H)

Example 43. (S)-quinuclidin-3-yl(6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.38 (m, 2H), 7.28 (m, 1H), 7.08 (m, 2H), 6.93(d, 1H), 5.03 (m, 1H), 4.91˜4.80 (m, 2H), 4.31 (s, 4H), 3.28 (m, 1H),2.22 (br, 1H), 2.06 (m, 2H), 1.87 (m, 3H), 1.71 (br, 1H), 1.61 (br, 1H),1.42 (br, 1H)

Example 44. (S)-quinuclidin-3-yl(6-(2,3-dihydrobenzofuran-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42˜7.27 (m, 5H), 6.85 (d, 1H), 5.05 (m, 1H),4.94˜4.80 (m, 2H), 4.63 (t, 2H), 3.28 (m, 3H), 2.86˜2.78 (m, 7H), 2.24(br, 1H), 2.06 (m, 2H), 1.88 (m, 3H), 1.71 (br, 1H), 1.61 (br, 1H), 1.41(br, 1H)

Example 45. (S)-quinuclidin-3-yl(6-(4-morpholinophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (d, 2H), 7.40 (m, 2H), 7.30 (m, 1H), 6.98(d, 2H), 5.07 (m, 1H), 4.95˜4.79 (m, 2H), 3.90 (m, 4H), 3.31 (m, 1H),3.23 (m, 4H), 2.86˜2.77 (m, 7H), 2.13 (m, 2H), 1.88 (m, 4H), 1.70 (br,1H), 1.59 (br, 1H), 1.39 (br, 1H)

Example 46. (S)-quinuclidin-3-yl(6-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (d, 2H), 7.40 (m, 3H), 7.28 (m, 1H), 6.98(d, 1H), 5.04 (m, 1H), 4.95˜4.81 (m, 1H), 3.86 (s, 3H), 3.29 (m, 1H),2.86˜2.79 (m, 7H), 2.30 (br, 1H), 2.09 (m, 2H), 1.88 (m, 3H), 1.72 (br,1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 47. (S)-quinuclidin-3-yl(6-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43 (m, 2H), 7.36 (m, 2H), 7.17 (d, 1H), 7.10(s, 1H), 6.91 (d, 1H), 5.07 (m, 1H), 4.96˜4.81 (m, 2H), 3.88 (s, 3H),3.31 (m, 1H), 2.87˜2.78 (m, 7H), 2.38 (br, 1H), 2.10 (m, 2H), 1.89 (m,3H), 1.71 (br, 1H), 1.60 (br, 1H), 1.41 (br, 1H)

Example 48. (S)-quinuclidin-3-yl(6-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.39 (m, 2H), 7.31˜7.28 (m, 3H), 7.01 (m, 2H),5.06 (m, 1H), 4.96˜4.81 (m, 2H), 3.83 (s, 3H), 3.29 (m, 1H), 2.86˜2.79(m, 7H), 2.30 (br, 1H), 2.07 (m, 2H), 1.88 (m, 3H), 1.72 (br, 1H), 1.62(br, 1H), 1.41 (br, 1H)

Example 49. (S)-quinuclidin-3-yl(6-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.53 (s, 1H), 8.45 (s, 1H), 7.48 (m, 2H), 7.38(m, 2H), 5.13 (m, 1H), 4.97˜4.79 (m, 2H), 3.26 (m, 1H), 2.86˜2.76 (m,7H), 2.05 (m, 2H), 1.81 (m, 4H), 1.70 (br, 1H), 1.59 (br, 1H), 1.40 (br,1H)

Example 50. (S)-quinuclidin-3-yl(6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.54 (m, 1H), 7.68 (m, 1H), 7.47 (m, 2H), 7.37(m, 2H), 4.99 (m, 2H), 4.80 (m, 1H), 3.29 (m, 1H), 2.88˜2.79 (m, 7H),2.63 (s, 3H), 2.09 (m, 2H), 1.89 (m, 4H), 1.72 (br, 1H), 1.61 (br, 1H),1.41 (br, 1H)

Example 51. (S)-quinuclidin-3-yl(6-(2-methoxypyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.21 (s, 1H), 7.44 (, 2H), 7.35 (s, 1H), 7.08(s, 1H), 6.93 (m, 1H), 5.04 (m, 1H), 4.96˜4.79 (m, 2H), 3.99 (s, 3H),3.27 (m, 1H), 2.86˜2.76 (m, 7H), 2.06 (m, 2H), 1.89 (m, 4H), 1.70 (br,1H), 1.58 (br, 1H), 1.40 (br, 1H)

Example 52. (S)-quinuclidin-3-yl(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 9.64 (br, 1H), 8.11 (s, 1H), 7.45 (m, 2H),7.31 (m, 1H), 7.12 (m, 2H), 6.56 (s, 1H), 5.21 (m, 1H), 4.97˜4.81 (m,2H), 3.29 (m, 1H), 3.87˜2.79 (m, 7H), 2.06 (m, 2H), 1.90 (m, 4H), 1.71(br, 1H), 1.62 (br, 1H), 1.42 (br, 1H)

Example 53. (S)-quinuclidin-3-yl(6-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 9.20 (s, 1H), 8.92 (s, 2H), 7.67 (m, 1H), 7.49(m, 1H), 7.40 (m, 1H), 5.09 (m, 1H), 4.98˜4.80 (m, 2H), 3.28 (m, 1H),2.87˜2.77 (m, 7H), 2.06 (m, 2H), 1.91 (m, 4H), 1.70 (br, 1H), 1.59 (br,1H), 1.40 (br, 1H)

Example 54. (S)-quinuclidin-3-yl(6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 9.84 (br, 1H), 8.37 (s, 1H), 7.60 (m, 1H),7.54 (s, 2H), 7.40 (s, 1H), 7.18 (m, 1H), 6.71 (s, 1H), 5.10 (m, 1H),5.01˜4.83 (m, 2H), 3.32 (m, 1H), 2.90˜2.84 (m, 7H), 2.14 (m, 2H), 1.93(m, 4H), 1.73 (br, 1H), 1.62 (br, 1H), 1.43 (br, 1H)

Examples 55 to 85

The titled compounds of Examples 55 to 85 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(7-bromo-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate prepared inPreparation 2; and the corresponding substituted-boronic acids,respectively.

Example 55. (S)-quinuclidin-3-yl(7-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.52 (d, 2H), 7.37 (d, 1H), 7.28 (m, 1H), 7.17(d, 1H), 7.11 (m, 2H), 4.98 (m, 2H), 4.78 (m, 1H), 3.25 (m, 1H),2.83˜2.70 (m, 7H), 2.04 (m, 2H), 1.89 (m, 3H), 1.78 (br, 1H), 1.68 (br,1H), 1.57 (br, 1H), 1.37 (br, 1H)

Example 56. (S)-quinuclidin-3-yl(7-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 3H), 7.39 (m, 3H), 7.17 (d, 1H), 4.99(m, 2H), 4.78 (m, 1H), 3.25 (m, 1H), 2.83˜2.70 (m, 7H), 2.05 (m, 2H),1.88 (m, 3H), 1.79 (br, 1H), 1.68 (br, 1H), 1.59 (br, 1H), 1.37 (br, 1H)

Example 57. (S)-quinuclidin-3-yl(7-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.44 (m, 3H), 7.23 (m, 2H), 7.15 (m, 2H), 5.10(m, 1H), 4.93 (m, 1H), 4.76 (m, 1H), 2.27 (m, 1H), 2.86˜2.72 (m, 7H),2.38 (s, 3H), 2.11 (m, 3H), 1.99˜1.86 (m, 3H), 1.66 (br, 1H), 1.56 (br,1H), 1.37 (br, 1H),

Example 58. (S)-quinuclidin-3-yl(7-(3-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.56 (d, 1H), 7.41 (m, 2H), 7.35 (m, 2H), 7.18(m, 1H), 7.04 (m, 1H), 5.13 (m, 1H), 4.97 (m, 1H), 4.60 (m, 1H), 3.28(m, 1H), 2.85˜2.75 (m, 7H), 2.24 (m, 1H), 2.08 (m, 1H), 1.89 (m, 3H),1.81 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.39 (br, 1H)

Example 59. (S)-quinuclidin-3-yl(7-(3-(chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.54 (s, 2H), 7.40˜7.28 (m, 4H), 7.20 (m, 1H),5.13 (m, 1H), 4.97 (m, 1H), 4.78 (m, 1H), 3.28 (m, 1H), 2.85˜2.75 (m,7H), 2.35 (br, 1H), 2.08 (m, 1H), 1.89 (m, 3H), 1.81 (br, 1H), 1.69 (br,1H), 1.59 (br, 1H), 1.40 (br, 1H)

Example 60. (S)-quinuclidin-3-yl(7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.78 (m, 1H), 7.73 (m, 1H), 7.55 (m, 3H), 7.42(m, 1H), 7.20 (d, 1H), 5.00 (m, 2H), 4.78 (m, 1H), 3.26 (m, 1H),2.84˜2.71 (m, 7H), 2.11 (m, 4H), 1.96 (m, 1H), 1.79 (br, 1H), 1.69 (br,1H), 1.58 (br, 1H), 1.39 (br, 1H)

Example 61. (S)-quinuclidin-3-yl(7-(2-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (m, 1H), 7.41 (m, 2H), 7.31 (m, 1H), 7.22(m, 3H), 5.20 (m, 1H), 4.97 (m, 1H), 4.76 (m, 1H), 3.26 (m, 1H),2.84˜2.69 (m, 7H), 2.31 (br, 1H), 2.08 (m, 1H), 1.88 (m, 3H), 1.80 (br,1H), 1.68 (br, 1H), 1.57 (br, 1H), 1.37 (br, 1H)

Example 62. (S)-quinuclidin-3-yl(7-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.44 (m, 2H), 7.30 (m, 4H), 7.16 (d, 1H), 5.17(m, 1H), 4.93 (m, 1H), 4.73 (m, 1H), 3.20 (m, 1H), 2.84˜2.67 (m, 7H),2.09 (m, 3H), 1.87 (m, 2H), 1.77 (br, 1H), 1.65 (br, 1H), 1.54 (br, 1H),1.35 (br, 1H)

Example 63. (S)-quinuclidin-3-yl(7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.73 (m, 1H), 7.56 (m, 1H), 7.45 (m, 1H), 7.30(m, 2H), 7.13 (m, 2H), 5.12 (m, 1H), 4.92 (m, 1H), 4.71 (m, 1H), 3.20(m, 1H), 2.82˜2.68 (m, 7H), 2.09 (m, 3H), 1.87 (m, 2H), 1.77 (br, 1H),1.64 (br, 1H), 1.53 (br, 1H), 1.33 (br, 1H)

Example 64. (S)-quinuclidin-3-yl(7-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 1H), 7.34 (m, 2H), 7.26˜7.16 (m, 3H),5.11 (m, 1H), 4.94 (m, 1H), 4.76 (m, 1H), 3.26 (m, 1H), 2.82˜2.69 (m,7H), 2.02 (m, 3H), 1.87 (m, 2H), 1.78 (br, 1H), 1.68 (br, 1H), 1.56 (br,1H), 1.36 (br, 1H)

Example 65. (S)-quinuclidin-3-yl(7-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (m, 1H), 7.36 (m, 2H), 7.16 (d, 1H), 6.92(m, 2H), 5.13 (m, 1H), 4.94 (m, 1H), 4.75 (m, 1H), 3.22 (m, 1H),2.83˜2.68 (m, 7H), 2.11 (m, 3H), 1.87 (m, 2H), 1.77 (br, 1H), 1.66 (br,1H), 1.55 (br, 1H), 1.35 (br, 1H)

Example 66. (S)-quinuclidin-3-yl(7-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.44 (m, 1H), 7.30˜7.17 (m, 3H), 7.01 (m, 1H),5.12 (m, 1H), 4.93 (m, 1H), 4.75 (m, 1H), 3.22 (m, 1H), 2.83˜2.68 (m,7H), 2.05 (m, 3H), 1.88 (m, 2H), 1.77 (br, 1H), 1.66 (br, 1H), 1.56 (br,1H), 1.36 (br, 1H)

Example 67. (S)-quinuclidin-3-yl(7-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (d, 1H), 7.35 (m, 1H), 7.18 (d, 1H), 7.11(m, 2H), 6.98 (m, 1H), 5.18 (m, 1H), 4.95 (m, 1H), 4.78 (m, 1H), 3.25(m, 1H), 2.85˜2.73 (m, 7H), 2.28 (br, 1H), 2.08 (m, 1H), 1.89 (m, 3H),1.80 (br, 1H), 1.67 (m, 1H), 1.57 (br, 1H), 1.38 (br, 1H)

Example 68. (S)-quinuclidin-3-yl(7-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.52 (m, 1H), 7.37 (m, 1H), 7.19 (d, 1H), 7.08(m, 2H), 6.78 (m, 1H), 5.08 (m, 1H), 4.97 (m, 1H), 4.80 (m, 1H), 3.28(m, 1H), 2.85˜2.76 (m, 7H), 2.09 (m, 2H), 1.93 (m, 1H), 1.89 (m, 2H),1.81 (br, 1H), 1.69 (br, 1H), 1.60 (br, 1H), 1.40 (br, 1H)

Example 69. (S)-quinuclidin-3-yl(7-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43 (m, 1H), 7.28 (m, 1H), 7.18 (d, 1H), 7.10(m, 1H), 7.03 (m, 1H), 5.27 (m, 1H), 4.94 (m, 1H), 4.76 (m, 1H), 3.23(m, 1H), 2.82˜2.66 (m, 7H), 2.07 (m, 3H), 1.88 (m, 2H), 1.81 (br, 1H),1.67 (br, 1H), 1.56 (br, 1H), 1.37 (br, 1H)

Example 70. (S)-quinuclidin-3-yl(7-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.63 (s, 1H), 7.48 (m, 2H), 7.38 (m, 2H), 7.18(d, 1H), 5.14 (m, 1H), 4.94 (m, 1H), 4.76 (m, 1H), 3.22 (m, 1H),2.83˜2.68 (m, 7H), 2.06 (m, 2H), 1.87 (m, 3H), 1.78 (br, 1H), 1.67 (m,1H), 1.56 (br, 1H), 1.37 (br, 1H)

Example 71. (S)-quinuclidin-3-yl(7-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.40 (m, 2H), 7.32 (m, 1H), 7.27 (m, 2H), 7.17(m, 1H), 5.12 (m, 1H), 4.96 (m, 1H), 4.76 (m, 1H), 3.26 (m, 1H),2.85˜2.69 (m, 7H), 2.11 (m, 3H), 1.89 (m, 2H), 1.78 (br, 1H), 1.67 (br,1H), 1.58 (br, 1H), 1.40 (br, 1H)

Example 72. (S)-quinuclidin-3-yl(7-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.65 (s, 2H), 7.62 (m, 1H), 7.50 (m, 3H), 7.25(d, 1H), 5.02 (m, 2H), 4.81 (br, 1H), 3.30 (m, 1H), 2.87˜2.72 (m, 7H),2.13 (m, 2H), 1.90 (m, 4H), 1.71 (br, 1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 73. (S)-quinuclidin-3-yl(7-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.82 (s, 1H), 8.59 (s, 1H), 7.87 (m, 1H), 7.58(m, 1H), 7.44 (m, 1H), 7.42 (m, 1H), 7.24 (d, 1H), 5.07 (m, 2H), 4.80(br, 1H), 3.27 (m, 1H), 2.87˜2.78 (m, 7H), 2.09˜1.99 (m, 5H), 1.82 (br,1H), 1.71 (br, 1H), 1.61 (br, 1H), 1.41 (br, 1H)

Example 74. (S)-quinuclidin-3-yl(7-(o-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.26 (m, 4H), 7.17 (s, 2H), 4.99(m, 2H), 4.77 (m, 1H), 3.29 (m, 1H), 2.85˜2.73 (m, 7H), 2.30 (s, 3H),2.14 (m, 4H), 1.90 (br, 1H), 1.80 (br, 1H), 1.69 (br, 1H), 1.58 (br,1H), 1.40 (br, 1H)

Example 75. (S)-quinuclidin-3-yl(7-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (m, 1H), 7.38 (d, 1H), 7.31 (m, 2H), 7.16(d, 1H), 7.05˜6.99 (m, 2H), 5.01 (m, 1H), 4.97 (m, 1H), 4.77 (br, 1H),3.83 (s, 3H), 3.25 (m, 1H), 2.84˜2.76 (m, 7H), 2.04 (m, 2H), 1.88 (m,4H), 1.69 (br, 1H), 1.58 (br, 1H), 1.40 (br, 1H)

Example 76. (S)-quinuclidin-3-yl(7-(2-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.59 (d, 1H), 7.43 (m, 1H), 7.32 (m, 2H), 7.15(d, 1H), 7.03˜6.97 (m, 2H), 5.00 (m, 1H), 4.97 (m, 1H), 4.76 (br, 1H),4.07 (m, 2H), 3.26 (m, 1H), 2.85˜2.76 (m, 7H), 2.06 (m, 2H), 1.89 (m,4H), 1.69 (br, 1H), 1.59 (br, 1H), 1.38 (t, 4H)

Example 77. (S)-quinuclidin-3-yl(7-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.57 (m, 1H), 7.50˜7.48 (m, 1H), 7.42 (m, 1H),7.18 (m, 2H), 7.14 (m, 1H), 6.88 (d, 1H), 4.99 (m, 2H), 4.79 (m, 1H),3.83 (s, 3H), 3.28 (m, 1H), 2.85˜2.78 (m, 7H), 2.06 (m, 2H), 1.89 (m,3H), 1.82 (br, 1H), 1.59 (br, 1H), 1.71 (br, 1H), 1.48 (br, 1H)

Example 78. (S)-quinuclidin-3-yl(7-(2-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.60 (m, 1H), 7.41 (d, 1H), 7.31 (m, 2H), 7.13(d, 1H), 6.99 (t, 1H), 4.99 (m, 1H), 4.93 (m, 1H), 4.77 (br, 1H), 4.54(m, 1H), 3.28 (m, 1H), 2.84˜2.75 (m, 7H), 2.13 (m, 2H), 2.06 (m, 3H),1.89 (m, 1H), 1.82 (br, 1H), 1.70 (br, 1H), 1.38 (br, 1H), 1.31 (d, 6H)

Example 79. (S)-quinuclidin-3-yl(7-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.67 (m, 1H), 7.50 (m, 3H), 7.40 (m, 1H), 7.17(m, 1H), 7.01 (m, 1H), 5.02 (m, 1H), 4.97˜4.78 (m, 2H), 4.18 (s, 2H),3.79 (s, 2H), 3.48 (s, 3H), 3.29 (m, 1H), 2.84˜2.76 (m, 7H), 2.05 (m,3H), 1.88 (m, 3H), 1.70 (br, 1H), 1.59 (br, 1H), 1.38 (br, 1H)

Example 80. (S)-quinuclidin-3-yl(7-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.52 (m, 3H), 7.41 (m, 1H), 7.17 (m, 1H), 6.99(m, 2H), 5.04 (m, 1H), 4.97 (m, 1H), 4.79 (m, 1H), 3.86 (s, 3H), 3.30(m, 1H), 2.88˜2.74 (m, 7H), 2.13 (m, 3H), 1.92 (m, 3H), 1.70 (br, 1H),1.60 (br, 1H), 1.40 (br, 1H)

Example 81. (S)-quinuclidin-3-yl(7-(4-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 3H), 7.40 (d, 1H), 7.16 (m, 1H), 6.97(m, 2H), 5.04 (m, 1H), 4.97 (m, 1H), 4.80 (m, 1H), 4.10 (m, 2H), 3.30(m, 1H), 2.88˜2.74 (m, 7H), 2.06 (m, 2H), 1.98 (m, 4H), 1.70 (br, 1H),1.60 (br, 1H), 1.40 (br, 1H), 1.39 (t, 3H)

Example 82. (S)-quinuclidin-3-yl(7-(4-propoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (m, 3H), 7.41 (d, 1H), 7.17 (m, 1H), 6.98(m, 2H), 5.01 (m, 1H), 4.97 (m, 1H), 4.79 (m, 1H), 3.97 (m, 2H), 3.28(m, 1H), 2.87˜2.76 (m, 7H), 2.06 (m, 2H), 1.84 (m, 6H), 1.69 (br, 1H),1.61 (br, 1H), 1.40 (br, 1H), 1.08 (t, 3H)

Example 83. (S)-quinuclidin-3-yl(7-(4-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.52 (m, 3H), 7.39 (d, 1H), 7.16 (d, 1H), 6.97(m, 2H), 5.04 (m, 1H), 4.97 (m, 1H), 4.79 (m, 1H), 4.59 (m, 1H), 3.27(m, 1H), 2.84˜2.71 (m, 7H), 2.05 (m, 2H), 1.93˜1.82 (m, 4H), 1.70 (br,1H), 1.60 (br, 1H), 1.38 (br, 1H), 1.17 (d, 6H)

Example 84. (S)-quinuclidin-3-yl(7-(benzo[d]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 1H), 7.35 (m, 1H), 7.16 (d, 1H), 7.05(m, 2H), 6.89 (m, 1H), 6.01 (s, 2H), 5.02 (m, 1H), 4.96 (m, 1H), 4.78(m, 1H), 3.31 (m, 1H), 2.87˜2.72 (m, 7H), 2.06 (m, 2H), 1.88 (m, 4H),1.70 (br, 1H), 1.60 (br, 1H), 1.28 (br, 1H)

Example 85. (S)-quinuclidin-3-yl(7-(m-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.57˜7.38 (m, 5H), 7.18 (m, 2H), 5.01 (m, 2H),4.78 (m, 1H), 3.29 (m, 1H), 2.86˜2.76 (m, 7H), 2.43 (s, 3H), 2.08 (m,2H), 1.89 (m, 4H), 1.62 (br, 1H), 1.59 (br, 1H), 1.38 (br, 1H)

Examples 86 to 150

The titled compounds of Examples 86 to 150 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(6-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateprepared in Preparation 3; and the corresponding substituted-boronicacids, respectively.

Example 86. (S)-quinuclidin-3-yl(6-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (m, 3H), 7.36 (m, 2H), 7.13 (t, 2H), 4.91(m, 2H), 4.65 (m, 1H), 3.37 (m, 1H), 3.05˜2.85 (m, 7H), 2.29 (m, 1H),1.96 (m, 1H), 1.83 (m, 1H), 1.72 (m, 3H), 1.36 (m, 1H), 1.17 (m, 3H),1.00 (s, 3H)

Example 87. (S)-quinuclidin-3-yl(6-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 2H), 7.41 (m, 2H), 7.31 (m, 3H), 4.90(m, 2H), 4.67 (m, 1H), 3.44 (m, 1H), 3.13˜3.88 (m, 7H), 2.20 (m, 1H),2.00 (m, 1H), 1.87 (m, 1H), 1.77 (m, 1H), 1.66 (m, 3H), 1.08 (m, 3H),1.00 (s, 3H)

Example 88. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (s, 4H), 7.48 (m, 1H), 7.38 (m, 2H),4.94˜4.87 (m, 2H), 4.68 (m, 1H), 3.40 (m, 1H), 3.11˜2.90 (m, 7H), 2.26(m, 1H), 1.85 (m, 1H), 1.73 (m, 1H), 1.58 (m, 3H), 1.40 (m, 1H), 1.08(m, 3H), 0.99 (m, 3H)

Example 89. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.68 (m, 1H), 7.58 (m, 2H), 7.50 (m, 1H), 7.39(m, 1H), 7.30 (m, 2H), 4.86 (m, 2H), 4.68 (m, 1H), 3.32 (m, 1H),3.00˜2.84 (m, 7H), 2.31 (br, 1H), 2.15 (m, 1H), 1.91 (m, 1H), 1.73 (br,1H), 1.66 (m, 2H), 1.50 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 90. (S)-quinuclidin-3-yl(6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.68 (m, 2H), 7.57 (m, 1H), 7.49 (m, 1H), 7.42(m, 3H), 7.05 (m, 1H), 4.86 (m, 2H), 4.68 (m, 1H), 3.37 (m, 1H),3.00˜2.88 (m, 7H), 2.16 (m, 2H), 1.95 (br, 1H), 1.77 (br, 1H), 1.64 (m,2H), 1.52 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 91. (S)-quinuclidin-3-yl(6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.55 (s, 1H), 7.45 (m, 1H), 7.31 (m, 5H), 4.85(m, 2H), 4.68 (m, 1H), 3.31 (m, 1H), 2.96˜2.83 (m, 7H), 2.33 (m, 1H),2.26 (m, 1H), 1.92 (br, 1H), 1.73 (m, 2H), 1.68 (br, 1H), 1.51 (br, 1H),1.08 (m, 3H), 0.98 (m, 3H)

Example 92. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.82 (s, 1H), 7.71 (m, 1H), 7.60 (m, 1H),7.48˜7.35 (m, 4H), 4.84 (m, 2H), 4.68 (m, 1H), 3.37 (m, 1H), 2.99˜2.83(m, 7H), 2.20 (m, 2H), 2.04 (br, 1H), 1.71 (m, 3H), 1.52 (br, 1H), 1.08(m, 3H), 0.99 (m, 3H)

Example 93. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 2H), 7.65 (m, 2H), 7.43 (m, 2H), 7.20(m, 1H), 4.85 (m, 2H), 4.68 (m, 1H), 3.40 (m, 1H), 3.06˜2.61 (m, 7H),2.22 (m, 1H), 2.10 (s, 1H), 1.96 (m, 1H), 1.82 (br, 1H), 1.73 (m, 2H),1.58 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 94. (S)-quinuclidin-3-yl(6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (m, 1H), 7.40 (m, 1H), 7.35 (m, 3H), 7.21(m, 1H), 7.15 (m, 1H), 4.89 (m, 2H), 4.68 (m, 1H), 3.38 (m, 1H),3.05˜2.71 (m, 7H), 2.22 (br, 1H), 2.10 (s, 1H), 1.96 (m, 1H), 1.80 (br,1H), 1.71 (m, 2H), 1.55 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 95. (S)-quinuclidin-3-yl(6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.48 (d, 1H), 7.32 (m, 5H), 7.19 (s, 1H), 4.87(m, 2H), 4.67 (m, 1H), 3.37 (m, 1H), 2.99˜2.86 (m, 7H), 2.38 (m, 2H),2.34 (m, 1H), 1.93 (m, 1H), 1.76 (m, 2H), 1.52 (br, 1H), 1.08 (m, 3H),0.99 (m, 3H)

Example 96. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.74 (m, 1H), 7.55 (m, 1H), 7.48 (m, 1H), 7.33(m, 2H), 7.15 (m, 1H), 7.07 (s, 1H), 4.92 (m, 2H), 4.68 (m, 1H), 3.40(m, 1H), 3.08˜2.62 (m, 7H), 2.26 (m, 1H), 2.10 (s, 1H), 1.99 (m, 1H),1.82 (m, 1H), 1.73 (m, 2H), 1.58 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 97. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.57 (m, 1H), 7.49 (m, 1H), 7.42(m, 1H), 7.37 (m, 2H), 7.21 (s, 1H), 4.89 (m, 2H), 4.68 (m, 1H), 3.33(m, 1H), 2.99˜2.86 (m, 7H), 2.31 (m, 1H), 2.18 (m, 1H), 1.99 (m, 1H),1.75 (m, 3H), 1.52 (m, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 98. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (m, 1H), 7.49 (m, 3H), 7.35 (s, 1H), 7.24(m, 2H), 5.39 (m, 2H), 4.67 (m, 1H), 3.38 (m, 1H), 3.00˜2.87 (m, 7H),2.41 (s, 3H), 2.04 (m, 3H), 1.96 (br, 1H), 1.73 (br, 2H), 1.50 (br, 1H),1.08 (m, 3H), 0.97 (m, 3H)

Example 99. (S)-quinuclidin-3-yl(6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.57 (m, 2H), 7.39 (m, 2H), 7.29 (m, 1H), 7.20(d, 2H), 6.75˜6.38 (t, 1H), 4.88 (m, 2H), 4.66 (m, 1H), 3.37 (m, 1H),2.98 (m, 7H), 2.24 (br, 1H), 1.95 (br, 1H), 1.76 (br, 1H), 1.72 (m, 3H),1.50 (m, 1H), 1.07 (m, 3H), 1.00 (m, 3H)

Example 100. (S)-quinuclidin-3-yl(6-(3,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.50 (m, 1H), 7.39 (m, 3H), 7.20(m, 1H), 4.85 (m, 2H), 4.67 (m, 1H), 3.36 (m, 1H), 3.00˜2.84 (m, 7H),2.33 (br, 1H), 2.17 (m, 1H), 1.90 (m, 1H), 1.77 (m, 2H), 1.70 (br, 1H),1.51 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 101. (S)-quinuclidin-3-yl(6-(2,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.50 (m, 1H), 7.38 (m, 2H), 6.94(m, 2H), 4.85 (m, 2H), 4.68 (m, 1H), 3.37 (m, 1H), 3.02˜2.78 (m, 7H),2.48 (br, 1H), 2.18 (m, 1H), 2.10 (s, 1H), 1.92 (br, 1H), 1.77 (m, 2H),1.52 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 102. (S)-quinuclidin-3-yl(6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.70 (m, 1H), 7.66 (m, 1H), 7.49 (m, 1H), 7.35(d, 1H), 7.15 (m, 2H), 4.88 (m, 2H), 4.68 (m, 1H), 3.33 (m, 1H),3.01˜2.81 (m, 7H), 2.59 (br, 1H), 2.25 (br, 1H), 1.82 (br, 1H), 1.76 (m,3H), 1.50 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 103. (S)-quinuclidin-3-yl(6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69˜7.49 (m, 1H), 7.35 (m, 2H), 7.13 (m, 2H),7.01 (m, 1H), 4.90 (m, 2H), 4.68 (m, 1H), 3.29 (m, 1H), 3.04˜2.81 (m,7H), 2.22 (m, 1H), 2.15 (m, 1H), 1.99 (m, 1H), 1.81 (br, 1H), 1.72 (m,2H), 1.53 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 104. (S)-quinuclidin-3-yl(6-(3,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.68˜7.49 (m, 1H), 7.39 (m, 2H), 7.09 (m, 2H),6.79 (m, 1H), 4.94 (m, 2H), 4.67 (m, 1H), 3.43 (m, 1H), 3.02˜2.88 (m,7H), 2.28 (m, 1H), 2.16 (m, 1H), 1.99 (br, 1H), 1.86 (br, 1H), 1.72 (m,2H), 1.50 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 105. (S)-quinuclidin-3-yl(6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 2H), 7.57 (m, 1H), 7.50 (m, 2H), 7.25(m, 1H), 4.89 (m, 2H), 4.66 (m, 1H), 3.33 (m, 1H), 3.02˜2.86 (m, 7H),2.37 (br, 2H), 2.10 (br, 1H), 1.92 (br, 1H), 1.77 (m, 2H), 1.50 (br,1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 106. (S)-quinuclidin-3-yl(6-(3,4-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 2H), 7.55 (m, 1H), 7.50 (m, 2H), 7.38(m, 1H), 4.86 (m, 2H), 4.68 (m, 1H), 3.39 (m, 1H), 3.04˜2.88 (m, 7H),2.26 (m, 2H), 2.04 (br, 1H), 1.99 (br, 1H), 1.78 (m, 2H), 1.53 (br, 1H),1.08 (m, 3H), 0.99 (m, 3H)

Example 107. (S)-quinuclidin-3-yl(6-(3,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.56 (m, 1H), 7.50 (m, 2H), 7.34(m, 2H), 4.85 (m, 2H), 4.68 (m, 1H), 3.31 (m, 1H), 2.98˜2.86 (m, 7H),2.14 (m, 2H), 1.94 (br, 1H), 1.73 (m, 2H), 1.65 (m, 1H), 1.51 (m, 1H),1.08 (m, 3H), 0.99 (m, 3H)

Example 108. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (m, 1H), 7.55 (m, 1H), 7.38 (m, 1H), 7.26(m, 1H), 7.02 (m, 1H), 4.86 (m, 2H), 4.67 (m, 1H), 3.30 (m, 1H),2.95˜2.87 (m, 7H), 2.51 (br, 2H), 2.08 (br, 1H), 1.73 (br, 1H), 1.64 (m,2H), 1.49 (br, 1H), 1.06 (m, 3H), 0.98 (m, 3H)

Example 109. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.68 (m, 1H), 7.54˜7.48 (m, 1H), 7.32 (m, 1H),7.24 (m, 1H), 7.12 (m, 1H), 4.91 (m, 2H), 4.67 (m, 1H), 3.44 (m, 1H),3.07 (m, 7H), 2.27 (br, 2H), 2.10 (br, 1H), 1.99 (br, 1H), 1.73 (m, 2H),1.63 (br, 1H), 1.08 (m, 3H), 0.98 (m, 3H)

Example 110. (S)-quinuclidin-3-yl(6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.29˜7.24 (m, 2H), 7.18 (d, 2H), 7.11 (m, 1H),6.98 (d, 2H), 4.85 (m, 1H), 4.80 (br, 1H), 4.66 (m, 1H), 4.17 (m, 2H),3.79 (m, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.59 (m,2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40(br, 1H), 1.05 (d, 3H), 0.96 (d, 3H)

Example 111. (S)-quinuclidin-3-yl(6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.23 (m, 3H), 7.11 (m, 1H), 6.91 (d, 1H),6.85 (m, 2H), 4.85 (m, 1H), 4.80 (br, 1H), 4.66 (m, 1H), 4.15 (m, 2H),3.78 (m, 2H), 3.47 (s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.59 (m,2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40(br, 1H), 1.05 (d, 3H), 0.96 (d, 3H)

Example 112. (S)-quinuclidin-3-yl(6-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32˜7.21 (m, 3H), 7.10 (m, 1H), 7.07 (m, 2H),6.96 (d, 1H), 4.88 (m, 1H), 4.79 (br, 1H), 4.66 (m, 1H), 4.12˜3.99 (m,2H), 3.53 (m, 2H), 3.25 (m, 1H), 3.22 (m, 3H), 2.88˜2.76 (m, 5H), 2.39(m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40(br, 1H), 1.05 (d, 3H), 0.96 (d, 3H)

Example 113. (S)-quinuclidin-3-yl(6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31 (m, 2H), 7.19 (d, 2H), 7.09 (m, 3H), 5.23(s, 2H), 4.88 (m, 1H), 4.79 (br, 1H), 4.66 (m, 1H), 3.31 (s, 3H), 3.25(m, 1H), 3.22 (m, 3H), 2.88˜2.76 (m, 5H), 2.39 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.05 (d, 3H),0.96 (d, 3H)

Example 114. (S)-quinuclidin-3-yl(6-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.23 (m, 3H), 7.11 (m, 1H), 6.91 (d, 1H),6.85 (m, 2H), 5.20 (s, 2H), 4.88 (m, 1H), 4.79 (br, 1H), 4.66 (m, 1H),3.30 (s, 3H), 3.25 (m, 1H), 3.22 (m, 3H), 2.88˜2.76 (m, 5H), 2.39 (m,2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40(br, 1H), 1.05 (d, 3H), 0.96 (d, 3H)

Example 115. (S)-quinuclidin-3-yl(6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32 (m, 1H), 7.31˜7.13 (m, 3H), 7.08 (m, 3H),5.05 (s, 2H), 4.88 (m, 1H), 4.79 (br, 1H), 4.66 (m, 1H), 3.34˜3.31 (m,3H), 3.29 (m, 1H), 3.22 (m, 3H), 2.88˜2.76 (m, 5H), 2.39 (m, 2H), 2.10(br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H),1.05 (d, 3H), 0.96 (d, 3H)

Example 116. (S)-quinuclidin-3-yl(6-(2-methoxypyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.20 (d, 1H), 7.37 (m, 1H), 7.27 (m, 1H), 7.06(m, 1H), 6.79 (m, 1H), 6.66 (s, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65(m, 1H), 3.98 (s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H),2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br,1H), 1.04 (m, 3H), 0.96 (m, 3H)

Example 117. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.54 (d, 1H), 7.36 (m, 1H), 7.27 (s, 2H), 7.04(s, 1H), 7.02 (d, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 3.25(m, 1H), 2.88˜2.76 (m, 5H), 2.57 (s, 3H), 2.56 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.05 (m, 3H),0.97 (m, 3H)

Example 118. (S)-quinuclidin-3-yl(6-(2-fluoropyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.26 (d, 1H), 7.38 (m, 1H), 7.27 (m, 2H), 7.08(m, 1H), 7.07 (m, 1H), 6.84 (s, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65(m, 1H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.05 (m, 3H),0.96 (m, 3H)

Example 119. (S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.78 (d, 1H), 7.62 (s, 1H), 7.44 (m, 2H), 7.31(m, 1H), 7.09 (m, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 3.25(m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H),1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.07 (m, 3H), 0.96 (m, 3H)

Example 120. (S)-quinuclidin-3-yl(6-(4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32 (m, 2H), 7.20 (m, 2H), 7.11 (m, 1H), 6.95(d, 2H), 4.87 (m, 2H), 4.65 (m, 1H), 3.86 (s, 3H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br,1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.05 (m, 3H), 0.96 (m, 3H)

Example 121. (S)-quinuclidin-3-yl(6-(3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 2H), 7.27 (m, 2H), 7.13 (m, 1H), 6.86(m, 2H), 6.81 (s, 1H), 4.87 (m, 2H), 4.65 (m, 1H), 3.84 (s, 3H), 3.25(m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H),1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.05 (m, 3H), 0.97 (m, 3H)

Example 122. (S)-quinuclidin-3-yl(6-(3-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34˜7.12 (m, 3H), 7.09 (m, 1H), 6.87 (d, 1H),6.84 (d, 1H), 6.81 (s, 1H), 4.87 (m, 2H), 4.65 (m, 1H), 4.01 (m, 2H),3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H), 1.85 (br,1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.45 (t, 3H), 1.05 (m,3H), 0.97 (m, 3H)

Example 123. (S)-quinuclidin-3-yl(6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.25 (m, 1H), 7.08 (m, 1H), 7.01(m, 2H), 6.87 (d, 1H), 4.91 (m, 1H), 4.87 (m, 1H), 4.65 (m, 1H), 3.87(s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.03 (m, 3H),0.97 (m, 3H)

Example 124. (S)-quinuclidin-3-yl(6-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.38 (d, 1H), 7.28 (m, 1H), 7.25 (m, 1H), 7.10(m, 1H), 6.79 (m, 2H), 4.91 (m, 1H), 4.85 (m, 1H), 4.66 (m, 1H), 3.86(s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.03 (m, 3H),0.97 (m, 3H)

Example 125. (S)-quinuclidin-3-yl(6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.37 (m, 2H), 7.26 (m, 1H), 7.03 (m, 1H), 6.86(m, 1H), 6.74 (m, 1H), 4.91 (m, 1H), 4.85 (m, 1H), 4.66 (m, 1H), 3.81(s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.03 (m, 3H),0.97 (m, 3H)

Example 126. (S)-quinuclidin-3-yl(6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34˜7.22 (m, 2H), 7.04 (m, 1H), 7.00 (m, 3H),4.91 (m, 1H), 4.85 (m, 1H), 4.66 (m, 1H), 3.94 (s, 3H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.56 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br,1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.03 (m, 3H), 0.97 (m, 3H)

Example 127. (S)-quinuclidin-3-yl(6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.26 (m, 2H), 7.18 (d, 1H), 7.10(m, 3H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.67 (m, 2H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br,1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.28 (t, 3H), 1.04 (m,3H), 0.96 (m, 3H)

Example 128. (S)-quinuclidin-3-yl(6-(3-(tert-butyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.39˜7.27 (m, 5H), 7.14 (m, 1H), 7.10 (d, 1H),4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 3.25 (m, 1H), 2.88˜2.76 (m,5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m,2H), 1.40 (br, 1H), 1.35 (s, 9H), 1.06 (m, 3H), 0.99 (m, 3H)

Example 129. (S)-quinuclidin-3-yl(6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35 (m, 2H), 7.26 (m, 2H), 7.20 (m, 1H), 7.11(s, 1H), 7.08 (m, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 3.25(m, 1H), 2.95 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.28 (d, 6H),1.06 (m, 3H), 0.99 (m, 3H)

Example 130. (S)-quinuclidin-3-yl(6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (m, 2H), 7.42 (m, 2H), 7.30 (m, 1H), 7.25(m, 1H), 7.10 (m, 2H), 6.84˜6.55 (t, 1H), 4.85 (m, 1H), 4.77 (m, 1H),4.67 (m, 1H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br,1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.06 (m,3H), 0.99 (m, 3H)

Example 131. (S)-quinuclidin-3-yl(6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.30 (m, 4H), 7.15 (m, 1H), 6.73 (m 1H), 6.63(m, 2H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.25 (m, 1H), 2.98(s, 6H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H),1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.06 (m, 3H), 0.99 (m, 3H)

Example 132. (S)-quinuclidin-3-yl(6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.30 (m, 4H), 7.12 (m, 1H), 6.87 (m 1H), 6.79(m, 2H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 4.57 (m, 1H), 3.25(m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H),1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.36 (d, 6H), 1.06 (m, 3H),0.99 (m, 3H)

Example 133. (S)-quinuclidin-3-yl(6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.30 (m, 1H), 7.25 (m, 1H), 7.11 (m, 2H), 6.95(d, 1H), 6.74 (m, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.92(s, 3H), 3.50 (m, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H),2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br,1H), 1.06 (m, 3H), 0.99 (m, 3H)

Example 134. (S)-quinuclidin-3-yl(6-(2,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.29 (m, 1H), 7.25 (m, 1H), 7.07 (m, 1H), 7.01(m, 1H), 6.55 (m, 2H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.86(s, 3H), 3.73 (m, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H),2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br,1H), 1.06 (m, 3H), 0.99 (m, 3H)

Example 135. (S)-quinuclidin-3-yl(6-(2,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.27 (m, 1H), 7.25 (m, 1H), 7.08 (m, 1H), 6.89(s, 2H), 6.70 (d, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.79(s, 3H), 3.69 (m, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H),2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br,1H), 1.06 (m, 3H), 0.99 (m, 3H)

Example 136. (S)-quinuclidin-3-yl(6-(2,6-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31 (m, 3H), 7.03 (m, 1H), 6.65 (d, 2H), 4.87(m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.72 (s, 6H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br,1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.03 (m, 3H), 0.95 (m, 3H)

Example 137. (S)-quinuclidin-3-yl(6-(3,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31 (m, 2H), 7.11 (m, 1H), 6.91 (d, 1H), 6.79(m, 2H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.93 (s, 3H), 3.89(s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.03 (m, 3H),0.95 (m, 3H)

Example 138. (S)-quinuclidin-3-yl(6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 2H), 7.11 (m, 1H), 6.46 (s, 1H), 6.41(s, 2H), 4.87 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.82 (s, 6H), 3.25(m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H),1.70 (br, 1H), 1.59 (m, 2H), 1.40 (br, 1H), 1.03 (m, 3H), 0.95 (m, 3H)

Example 139. (S)-quinuclidin-3-yl(6-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.20 (m, 3H), 7.14 (d, 1H), 7.08 (m, 1H),6.97 (d, 1H), 4.89 (m, 1H), 4.77 (m, 1H), 4.67 (m, 1H), 3.94 (s, 3H),3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.57 (m, 2H), 2.10 (br, 1H), 1.85 (br,1H), 1.70 (br, 1H), 1.61 (br, 3H), 1.42 (br, 1H), 1.03 (m, 3H), 0.95 (m,3H)

Example 140. (S)-quinuclidin-3-yl(6-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.20 (m, 3H), 7.11 (d, 2H), 6.95 (d, 1H),4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 4.13 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.93 (br, 1H), 1.85 (br,1H), 1.70 (br, 1H), 1.61 (br, 3H), 1.48 (t, 3H), 1.42 (br, 1H), 1.03 (m,3H), 0.95 (m, 3H)

Example 141. (S)-quinuclidin-3-yl(6-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31˜7.21 (m, 3H), 7.08 (m, 2H), 6.95 (d, 1H),4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 4.02 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.93 (br, 1H), 1.87 (m,2H), 1.85 (br, 1H), 1.70 (br, 1H), 1.61 (br, 3H), 1.42 (br, 1H), 1.10(t, 3H), 1.03 (m, 3H), 0.95 (m, 3H)

Example 142. (S)-quinuclidin-3-yl(6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.22 (m, 2H), 7.08 (m, 1H), 7.00 (m, 2H),6.97 (m, 1H), 4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 4.57 (m, 1H),3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br,1H), 1.70 (br, 1H), 1.61 (br, 3H), 1.40 (d, 6H), 1.03 (m, 3H), 0.94 (m,3H)

Example 143. (S)-quinuclidin-3-yl(6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31˜7.22 (m, 3H), 7.08 (m, 2H), 6.97 (d, 1H),4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 4.06 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (m, 3H), 1.70 (br,1H), 1.59 (m, 5H), 1.40 (br, 1H), 1.05 (m, 3H), 1.03 (t, 3H), 0.95 (m,3H)

Example 144. (S)-quinuclidin-3-yl(6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.22 (m, 2H), 7.08 (m, 1H), 6.99 (m, 3H),4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 4.17 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br,1H), 1.59 (m, 3H), 1.48 (t, 3H), 1.40 (br, 1H), 1.04 (m, 3H), 0.96 (m,3H)

Example 145. (S)-quinuclidin-3-yl(6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33˜7.22 (m, 2H), 7.08 (m, 1H), 6.99 (m, 3H),4.87 (m, 1H), 4.77 (m, 1H), 4.65 (m, 1H), 4.05 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.10 (br, 1H), 1.88 (m, 2H), 1.85 (br,1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.08 (t, 3H), 1.04 (m,3H), 0.96 (m, 3H)

Example 146. (S)-quinuclidin-3-yl(6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.28˜7.20 (m, 2H), 7.07 (m, 1H), 6.89 (s, 2H),4.86 (m, 1H), 4.78 (m, 1H), 4.65 (m, 1H), 3.78 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.31 (s, 6H), 2.10 (br, 1H), 1.88 (m,2H), 1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.12 (t,3H), 1.04 (m, 3H), 0.96 (m, 3H)

Example 147. (S)-quinuclidin-3-yl(6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.28˜7.20 (m, 2H), 7.08 (m, 1H), 6.89 (s, 2H),4.86 (m, 1H), 4.78 (m, 1H), 4.65 (m, 1H), 3.80 (m, 2H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.58 (m, 2H), 2.31 (s, 6H), 2.10 (br, 1H), 1.85 (m,3H), 1.70 (br, 1H), 1.59 (m, 5H), 1.40 (br, 1H), 1.05 (m, 3H), 1.01 (t,3H), 0.95 (m, 3H)

Example 148. (S)-quinuclidin-3-yl(6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35 (m, 1H), 7.25 (m, 1H), 7.08 (m, 2H), 6.77(d, 1H), 6.68 (d, 1H), 4.86 (m, 1H), 4.80 (m, 1H), 4.68 (m, 1H), 3.84(s, 3H), 3.25 (m, 1H), 2.88˜2.76 (m, 5H), 2.55 (br, 2H), 2.10 (br, 1H),1.85 (br, 1H), 1.70 (br, 1H), 1.59 (m, 3H), 1.40 (br, 1H), 1.05 (m, 3H),0.95 (m, 3H)

Example 149. (S)-quinuclidin-3-yl(6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32˜7.21 (m, 3H), 7.07 (m, 2H), 6.97 (d, 1H),4.89 (m, 1H), 4.80 (m, 1H), 4.68 (m, 1H), 4.59 (m, 1H), 3.25 (m, 1H),2.88˜2.76 (m, 5H), 2.55 (m, 2H), 2.10 (br, 1H), 1.85 (br, 1H), 1.70 (br,1H), 1.59 (m, 3H), 1.40 (d, 7H), 1.03 (m, 3H), 0.96 (m, 3H)

Example 150. (S)-quinuclidin-3-yl(6-(2-acetylthiophen-3-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.62 (d, 1H), 7.37 (m, 1H), 7.26 (m, 1H), 7.09(m, 1H), 6.93 (m, 1H), 4.80 (m, 1H), 4.70 (m, 1H), 4.67 (m, 1H), 3.25(m, 1H), 2.88˜2.76 (m, 5H), 2.44 (m, 2H), 2.10 (br, 1H), 1.95 (m, 3H),1.85 (br, 1H), 1.70 (br, 1H), 1.61 (br, 1H), 1.42 (br, 1H), 1.01 (m,3H), 0.89 (m, 3H)

Examples 151 to 170

The titled compounds of Examples 151 to 170 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(7-bromo-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateprepared in Preparation 4; and the corresponding substituted-boronicacids, respectively.

Example 151. (S)-quinuclidin-3-yl(7-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (m, 2H), 7.46 (m, 1H), 7.38 (m, 1H), 7.18(m, 1H), 7.11 (m, 2H), 4.83 (m, 2H), 4.68 (m, 1H), 3.30 (m, 1H),2.99˜2.81 (m, 7H), 2.14 (m, 1H), 1.99 (m, 1H), 1.89 (m, 1H), 1.74 (m,2H), 1.64 (m, 1H), 1.37 (m, 1H), 1.12 (m, 3H), 1.08 (s, 3H)

Example 152. (S)-quinuclidin-3-yl(7-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.56 (m, 1H), 7.48 (m, 3H), 7.42 (m, 2H), 7.20(d, 1H), 4.84 (m, 2H), 4.66 (m, 1H), 3.32 (m, 1H), 2.98˜2.85 (m, 7H),2.12 (m, 2H), 1.86 (m, 1H), 1.72 (m, 2H), 1.64 (m, 1H), 1.51 (m, 1H),1.08 (m, 3H), 0.99 (s, 3H)

Example 153. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.66 (m, 4H), 7.51˜7.42 (m, 2H), 7.23 (m, 1H),4.85˜4.81 (m, 2H), 4.68 (m, 1H), 3.29 (m, 1H), 2.88˜2.75 (m, 7H), 2.26(m, 1H), 2.09 (m, 1H), 1.84 (m, 1H), 1.73 (m, 2H), 1.61 (m, 1H), 1.43(m, 1H), 1.08 (m, 3H), 0.99 (s, 3H)

Example 154. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.55 (m, 2H), 7.48 (m, 2H), 7.39(m, 1H), 7.19 (m, 1H), 4.84 (m, 2H), 4.68 (m, 1H), 3.30 (m, 1H), 2.85(m, 7H), 2.23˜2.14 (m, 2H), 1.85 (m, 1H), 1.72 (m, 2H), 1.63 (m, 1H),1.44 (m, 1H), 1.08 (m, 3H), 0.99 (s, 3H)

Example 155. (S)-quinuclidin-3-yl(7-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.56 (m, 1H), 7.45 (m, 2H), 7.39(m, 1H), 7.26 (m, 1H), 7.03 (m, 1H), 4.87 (m, 2H), 4.69 (m, 1H), 3.31(m, 1H), 2.87˜2.73 (m, 7H), 2.09 (m, 2H), 1.84 (m, 1H), 1.72 (m, 2H),1.61 (br, 1H), 1.43 (br, 1H), 1.09 (m, 3H), 0.99 (m, 3H)

Example 156. (S)-quinuclidin-3-yl(7-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53˜7.31 (m, 6H), 7.20 (m, 1H), 4.83 (m, 2H),4.68 (m, 1H), 3.33 (m, 1H), 2.88˜2.81 (m, 7H), 2.09 (m, 2H), 1.86 (br,1H), 1.72 (m, 2H), 1.62 (br, 1H), 1.46 (br, 1H), 1.09 (m, 3H), 0.99 (m,3H)

Example 157. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.80 (m, 2H), 7.56 (m, 2H), 7.51 (m, 1H), 7.43(m, 1H), 7.22 (m, 1H), 4.87 (m, 2H), 4.69 (m, 1H), 3.30 (m, 1H),2.88˜2.77 (m, 7H), 2.13 (m, 2H), 1.86 (m, 1H), 1.73 (m, 2H), 1.62 (br,1H), 1.42 (br, 1H), 1.09 (m, 3H), 0.99 (m, 3H)

Example 158. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.48 (m, 3H), 7.40 (m, 2H), 7.21 (m, 2H), 4.86(m, 2H), 4.71 (m, 1H), 3.32 (m, 1H), 2.92˜2.86 (m, 7H), 2.17 (br, 1H),2.10 (m, 2H), 1.90 (m, 1H), 1.70 (br, 1H), 1.66 (br, 1H), 1.47 (br, 1H),1.09 (m, 3H), 0.99 (m, 3H)

Example 159. (S)-quinuclidin-3-yl(7-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.47 (m, 3H), 7.21 (m, 2H), 7.16(m, 1H), 4.86 (m, 2H), 4.69 (m, 1H), 3.30 (m, 1H), 2.89˜2.81 (m, 7H),2.13 (m, 2H), 1.86 (br, 1H), 1.72 (m, 2H), 1.62 (br, 1H), 1.45 (br, 1H),1.09 (m, 3H), 1.00 (m, 3H)

Example 160. (S)-quinuclidin-3-yl(7-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 1H), 7.55 (m, 2H), 7.31 (m, 3H), 7.17(m, 1H), 4.85 (m, 2H), 4.69 (m, 1H), 3.30 (m, 1H), 2.87˜2.77 (m, 7H),2.19 (m, 2H), 1.86 (m, 1H), 1.72 (m, 2H), 1.60 (br, 1H), 1.41 (br, 1H),1.09 (m, 3H), 1.00 (m, 3H)

Example 161. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.74 (m, 1H), 7.56 (m, 1H), 7.48 (m, 1H), 7.33(m, 1H), 7.26 (m, 1H), 7.15 (s, 2H), 4.82 (m, 2H), 4.67 (m, 1H), 3.29(m, 1H), 2.87˜2.72 (m, 7H), 2.20 (m, 2H), 1.86 (br, 1H), 1.72 (m, 2H),1.59 (br, 1H), 1.43 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 162. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (m, 2H), 7.48 (m, 4H), 7.18 (m, 1H), 4.81(m, 2H), 4.68 (m, 1H), 3.30 (m, 1H), 2.87˜2.77 (m, 7H), 2.10 (m, 2H),1.86 (br, 1H), 1.73 (m, 2H), 1.61 (br, 1H), 1.45 (br, 1H), 1.08 (m, 3H),0.99 (m, 3H)

Example 163. (S)-quinuclidin-3-yl(2,2-dimethyl-7-(2-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.93 (m, 1H), 7.45 (m, 2H), 7.21 (m, 4H), 4.84(m, 2H), 4.68 (m, 1H), 3.12 (m, 1H), 2.98˜2.84 (m, 7H), 2.40 (s, 3H),2.16 (m, 1H), 2.13 (m, 1H), 1.93 (br, 1H), 1.72 (m, 2H), 1.63 (br, 1H),1.47 (br, 1H), 1.07 (m, 3H), 0.98 (m, 3H)

Example 164. (S)-quinuclidin-3-yl(7-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.71 (m, 2H), 7.55 (m, 1H), 7.37 (m, 1H), 7.20(s, 3H), 6.74˜6.38 (t, 1H), 4.84 (m, 2H), 4.69 (m, 1H), 3.21 (m, 1H),2.91˜2.81 (m, 7H), 2.22 (m, 2H), 1.89 (br, 1H), 1.72 (m, 2H), 1.64 (br,1H), 1.47 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 165. (S)-quinuclidin-3-yl(7-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 3H), 7.40 (m, 1H), 7.17 (m, 1H), 7.09(m, 1H), 7.01 (m, 1H), 4.90˜4.80 (m, 2H), 4.67 (m, 1H), 4.18 (s, 2H),3.79 (s, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 2.91˜2.76 (m, 7H), 2.10 (m,2H), 1.88 (br, 1H), 1.71 (br, 2H), 1.60 (br, 1H), 1.40 (br, 1H), 1.08(m, 3H), 0.98 (m, 3H)

Example 166. (S)-quinuclidin-3-yl(7-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.46 (m, 1H), 7.41 (m, 1H), 7.34 (m, 1H), 7.18(m, 3H), 6.90 (d, 1H), 4.90˜4.80 (m, 2H), 4.67 (m, 1H), 4.18 (s, 2H),3.79 (m, 2H), 3.48 (m, 3H), 3.27 (m, 1H), 2.86˜2.72 (m, 7H), 2.10 (m,2H), 1.88 (br, 1H), 1.73 (br, 2H), 1.60 (br, 1H), 1.40 (br, 1H), 1.07(m, 3H), 0.98 (m, 3H)

Example 167. (S)-quinuclidin-3-yl(7-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.48 (d, 1H), 7.41 (d, 1H), 7.28 (m, 2H), 7.12(m, 1H), 7.04 (m, 2H), 4.98 (d, 1H), 4.76 (br, 1H), 4.67 (d, 1H), 4.12(m, 2H), 3.70 (m, 2H), 3.37 (s, 3H), 3.26 (m, 1H), 2.85˜2.76 (m, 7H),2.10 (m, 2H), 1.88 (br, 1H), 1.73 (br, 2H), 1.60 (br, 1H), 1.40 (br,1H), 1.07 (m, 3H), 0.98 (m, 3H)

Example 168. (S)-quinuclidin-3-yl(7-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.48 (m, 3H), 7.37 (d, 1H), 7.16 (d, 1H), 7.09(m, 2H), 5.22 (s, 2H), 4.80 (m, 2H), 4.67 (d, 1H), 3.51 (s, 3H), 3.27(m, 1H), 2.87˜2.72 (m, 7H), 2.22 (m, 2H), 1.89 (br, 1H), 1.72 (m, 2H),1.64 (br, 1H), 1.47 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 169. (S)-quinuclidin-3-yl(7-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.49 (m, 1H), 7.39 (d, 1H), 7.33 (m, 1H),7.23˜7.16 (m, 3H), 7.02 (d, 1H), 5.23 (s, 2H), 4.81 (m, 2H), 4.67 (d,1H), 3.51 (s, 3H), 3.27 (m, 1H), 2.87˜2.72 (m, 7H), 2.22 (m, 2H), 1.89(br, 1H), 1.72 (m, 2H), 1.64 (br, 1H), 1.47 (br, 1H), 1.08 (m, 3H), 0.99(m, 3H)

Example 170. (S)-quinuclidin-3-yl(7-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.55 (m, 1H), 7.49 (m, 1H), 7.37 (m, 1H), 7.26(m, 2H), 7.20 (m, 1H), 7.07 (m, 1H), 5.13 (m, 2H), 4.84 (m, 2H), 4.69(m, 1H), 3.43 (s, 3H), 3.25 (m, 1H), 2.91˜2.74 (m, 7H), 2.22 (m, 2H),1.89 (br, 1H), 1.72 (m, 2H), 1.64 (br, 1H), 1.47 (br, 1H), 1.08 (m, 3H),0.99 (m, 3H)

Examples 171 to 185

The titled compounds of Examples 171 to 185 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(7′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamateprepared in Preparation 6; and the corresponding substituted-boronicacids, respectively.

Example 171. (S)-quinuclidin-3-yl(7′-(4-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (m, 3H), 7.40 (d, 1H), 7.23 (d, 1H), 7.13(m, 2H), 5.15 (br, 1H), 4.76 (br, 1H), 4.32 (m, 1H), 3.26 (m, 1H),2.94˜2.72 (m, 7H), 2.13 (m, 3H), 1.79 (br, 1H), 1.67 (br, 1H), 1.58 (br,1H), 1.38 (br, 1H), 0.92 (m, 1H), 0.58 (m, 1H), 0.49 (m, 2H)

Example 172. (S)-quinuclidin-3-yl(7′-(4-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.49 (m, 2H), 7.41 (m, 4H), 7.24 (d, 1H), 5.17(br, 1H), 4.76 (m, 1H), 4.33 (m, 1H), 3.26 (m, 1H), 2.91˜2.73 (m, 7H),2.09 (m, 3H), 1.79 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.38 (br,1H), 0.92 (m, 1H), 0.58 (m, 1H), 0.49 (m, 2H)

Example 173. (S)-quinuclidin-3-yl(7′-(4-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (s, 4H), 7.56 (d, 1H), 7.46 (d, 1H), 7.25(m, 1H), 5.18 (br, 1H), 4.77 (m, 1H), 4.34 (m, 1H), 3.27 (m, 1H),2.92˜2.73 (m, 7H), 2.14 (m, 3H), 1.79 (br, 1H), 1.69 (br, 1H), 1.58 (br,1H), 1.38 (br, 1H), 0.92 (m, 1H), 0.58 (m, 1H), 0.50 (m, 2H)

Example 174. (S)-quinuclidin-3-yl(7′-(4-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.58 (m, 2H), 7.50 (m, 1H), 7.43 (d, 1H), 7.28(m, 3H), 5.17 (br, 1H), 4.76 (m, 1H), 4.33 (m, 1H), 3.29 (m, 1H),2.90˜2.78 (m, 7H), 2.13 (m, 3H), 1.79 (br, 1H), 1.69 (br, 1H), 1.59 (br,1H), 1.39 (br, 1H), 0.92 (m, 1H), 0.58 (m, 1H), 0.49 (m, 2H)

Example 175. (S)-quinuclidin-3-yl(7′-(3-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.53 (d, 1H), 7.44˜7.35 (m, 3H), 7.24 (t, 2H),7.04 (t, 1H), 5.20 (m, 1H), 4.77 (m, 1H), 4.34 (m, 1H), 3.27 (m, 1H),2.94˜2.73 (m, 7H), 2.06 (m, 3H), 1.82 (br, 1H), 1.70˜1.67 (br, 1H), 1.58(br, 1H), 1.41 (br, 1H), 0.92 (m, 1H), 0.58 (br, 1H), 0.49 (m, 2H)

Example 176. (S)-quinuclidin-3-yl(7′-(3-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.69 (t, 1H), 7.55˜7.41 (m, 4H), 7.36 (m, 1H),7.23 (d, 1H), 5.16 (m, 1H), 4.77 (m, 1H), 4.35 (m, 1H), 3.26 (m, 1H),2.90˜2.73 (m, 7H), 2.06 (m, 3H), 1.79 (br, 1H), 1.69 (br, 1H), 1.59 (br,1H), 1.39 (br, 1H), 0.93 (m, 1H), 0.58 (m, 1H), 0.49 (m, 2H)

Example 177. (S)-quinuclidin-3-yl(7′-(3-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.79 (m, 2H), 7.55 (m, 3H), 7.45 (m, 1H), 7.27(m, 1H), 5.17 (m, 1H), 4.77 (m, 1H), 3.35 (m, 1H), 3.26 (m, 1H),2.92˜2.74 (m, 7H), 2.13 (br, 1H), 2.08 (m, 2H), 1.81 (br, 1H), 1.69 (br,1H), 1.59 (br, 1H), 1.39 (br, 1H), 0.92 (m, 1H), 0.59 (m, 1H), 0.50 (m,2H)

Example 178. (S)-quinuclidin-3-yl(7′-(3-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.54˜7.41 (m, 5H), 7.26 (m, 1H), 7.27 (m, 1H),5.16 (m, 1H), 4.77 (m, 1H), 4.35 (m, 1H), 3.26 (m, 1H), 2.94˜2.74 (m,7H), 2.18 (br, 1H), 2.07 (m, 2H), 1.80 (br, 1H), 1.70 (br, 1H), 1.59(br, 1H), 1.39 (br, 1H), 0.93 (m, 1H), 0.58 (m, 1H), 0.50 (m, 2H)

Example 179. (S)-quinuclidin-3-yl(7′-(2-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.49 (m, 1H), 7.41 (m, 2H), 7.32 (m, 1H), 7.24(m, 2H), 7.15 (m, 1H), 5.18 (m, 1H), 4.76 (m, 1H), 4.35 (m, 1H), 3.27(m, 1H), 2.91˜2.73 (m, 7H), 2.13 (m, 1H), 2.08 (d, 2H), 1.82 (br, 1H),1.69 (br, 1H), 1.59 (br, 1H), 1.43 (br, 1H), 0.93 (m, 1H), 0.60 (m, 1H),0.49 (m, 2H)

Example 180. (S)-quinuclidin-3-yl(7′-(2-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.48 (d, 1H), 7.41 (d, 1H), 7.33 (m, 4H), 7.22(m, 1H), 5.19 (m, 1H), 4.74 (m, 1H), 4.14 (m, 1H), 3.23 (m, 1H),2.95˜2.68 (m, 7H), 2.13 (m, 3H), 1.80 (br, 1H), 1.68 (br, 1H), 1.57 (br,1H), 1.39 (br, 1H), 0.90 (m, 1H), 0.59 (m, 1H), 0.49 (m, 2H)

Example 181. (S)-quinuclidin-3-yl(7′-(2-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.75 (d, 1H), 7.56 (m, 1H), 7.46 (m, 1H), 7.33(m, 2H), 7.18 (s, 2H), 5.14 (m, 1H), 4.73 (m, 1H), 4.32 (m, 1H), 3.23(m, 1H), 2.95˜2.69 (m, 7H), 2.09 (m, 3H), 1.81 (br, 1H), 169 (br, 1H),1.56 (br, 1H), 1.38 (br, 1H), 0.89 (m, 1H), 0.59 (m, 1H), 0.49 (m, 2H)

Example 182. (S)-quinuclidin-3-yl(7′-(2-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.43˜7.31 (m, 6H), 7.20 (m, 1H), 5.15 (m, 1H),4.75 (m, 1H), 4.33 (m, 1H), 3.27 (m, 1H), 2.95˜2.63 (m, 7H), 2.09 (m,3H), 1.81 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.39 (br, 1H), 0.93(m, 1H), 0.57 (m, 1H), 0.49 (m, 2H)

Example 183. (S)-quinuclidin-3-yl(7′-(p-tolyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.70 (m, 1H), 7.57˜7.46 (m, 4H), 7.28˜7.21 (m,2H), 5.15 (m, 1H), 4.77 (m, 1H), 4.34 (m, 1H), 3.26 (m, 1H), 2.90˜2.68(m, 7H), 2.40 (s, 3H), 2.13 (m, 3H), 1.81 (br, 1H), 1.69 (br, 1H), 1.59(br, 1H), 1.39 (br, 1H), 0.94 (m, 1H), 0.58 (m, 1H), 0.48 (m, 2H)

Example 184. (S)-quinuclidin-3-yl(7′-(4-(difluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.56 (m, 3H), 7.42 (m, 1H), 7.22 (m, 3H),6.74˜6.37 (t, 1H), 5.16 (m, 1H), 4.76 (m, 1H), 4.33 (m, 1H), 3.26 (m,1H), 2.90˜2.67 (m, 7H), 2.06 (m, 3H), 1.75 (br, 1H), 1.69 (br, 1H), 1.59(br, 1H), 1.38 (br, 1H), 0.92 (m, 1H), 0.57 (br, 1H), 0.49 (m, 2H)

Example 185. (S)-quinuclidin-3-yl(7′-(4-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50 (m, 3H), 7.40 (d, 1H), 7.19 (d, 1H), 7.11(m, 2H), 5.22 (s, 2H), 5.13 (m, 1H), 4.74 (br, 1H), 4.33 (d, 1H), 3.51(s, 3H), 3.25 (m, 1H), 2.88˜2.67 (m, 7H), 2.05 (br, 2H), 1.75 (br, 1H),1.68 (br, 1H), 1.58 (br, 1H), 1.37 (br, 1H), 1.26 (br, 1H), 0.93 (m,1H), 0.57 (br, 1H), 0.47 (m, 2H)

Examples 186 to 226

The titled compounds of Examples 186 to 226 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(6′-bromo-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamateprepared in Preparation 5; and the corresponding substituted-boronicacids, respectively.

Example 186. (S)-quinuclidin-3-yl(6′-(4-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.36 (m, 1H), 7.32 (m, 1H), 7.23 (m, 2H), 7.13(d, 2H), 7.08 (m, 1H), 5.13 (m, 1H), 4.78 (br, 1H), 4.31 (d, 1H), 3.25(m, 1H), 2.85˜2.76 (m, 7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H),1.69 (br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m,1H), 0.58 (m, 1H), 0.45 (m, 2H)

Example 187. (S)-quinuclidin-3-yl(6′-(4-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.37 (d, 2H), 7.33 (m, 1H), 7.25 (m, 3H), 7.12(m, 1H), 5.13 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 3.25 (m, 1H),2.85˜2.76 (m, 7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69(br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H),0.58 (m, 1H), 0.45 (m, 2H)

Example 188. (S)-quinuclidin-3-yl(6′-(4-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.68 (d, 2H), 7.40 (d, 2H), 7.25 (m, 2H), 7.12(m, 1H), 5.13 (m, 1H), 4.77 (br, 1H), 4.36 (d, 1H), 3.25 (m, 1H),2.85˜2.76 (m, 7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69(br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H),0.58 (m, 1H), 0.45 (m, 2H)

Example 189. (S)-quinuclidin-3-yl(6′-(4-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.58 (m, 1H), 7.35 (d, 2H), 7.29˜7.25 (m, 3H),7.12 (m, 1H), 5.15 (m, 1H), 4.77 (br, 1H), 4.36 (d, 1H), 3.25 (m, 1H),2.85˜2.76 (m, 7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69(br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H),0.58 (m, 1H), 0.45 (m, 2H)

Example 190. (S)-quinuclidin-3-yl(6′-(3-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.39 (m, 3H), 7.15 (m, 1H), 7.09˜7.01 (m, 3H),5.14 (m, 1H), 4.78 (br, 1H), 4.35 (d, 1H), 3.25 (m, 1H), 2.85˜2.74 (m,7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.59(br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H), 0.56 (m, 1H), 0.42(m, 2H)

Example 191. (S)-quinuclidin-3-yl(6′-(3-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.38˜7.26 (m, 5H), 7.19 (m, 1H), 7.12 (m, 1H),5.14 (m, 1H), 4.78 (br, 1H), 4.36 (d, 1H), 3.25 (m, 1H), 2.85˜2.74 (m,7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.59(br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H), 0.59 (m, 1H), 0.46(m, 2H)

Example 192. (S)-quinuclidin-3-yl(6′-(3-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.62 (m, 1H), 7.56 (m, 2H), 7.39 (m, 1H), 7.29(m, 2H), 7.13 (m, 1H), 5.14 (m, 1H), 4.78 (br, 1H), 4.36 (d, 1H), 3.25(m, 1H), 2.85˜2.74 (m, 7H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H),1.69 (br, 1H), 1.60 (br, 1H), 1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m,1H), 0.59 (m, 1H), 0.48 (m, 2H)

Example 193. (S)-quinuclidin-3-yl(6′-(3-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.50˜7.26 (m, 3H), 7.25˜7.13 (m, 4H), 5.14 (m,1H), 4.78 (br, 1H), 4.35 (d, 1H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.05(br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.60 (br, 1H),1.35 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H), 0.59 (m, 1H), 0.47 (m, 2H)

Example 194. (S)-quinuclidin-3-yl(6′-(4-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32˜7.25 (m, 2H), 7.22 (d, 2H), 7.15 (m, 1H),6.98 (d, 2H), 5.12 (m, 1H), 4.76 (br, 1H), 4.37 (d, 1H), 4.18 (d, 2H),3.79 (d, 2H), 3.48 (s, 3H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.05 (br,1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.35(br, 1H), 1.10 (br, 1H), 0.89 (m, 1H), 0.56 (m, 1H), 0.42 (m, 2H)

Example 195. (S)-quinuclidin-3-yl(6′-(3-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35˜7.25 (m, 3H), 7.15 (m, 1H), 6.93 (d, 1H),6.87 (s, 2H), 5.14 (m, 1H), 4.76 (br, 1H), 4.35 (d, 1H), 4.15 (d, 2H),3.78 (d, 2H), 3.47 (s, 3H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.05 (br,1H), 1.94 (br, 1H), 1.80 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.38(br, 1H), 1.14 (br, 1H), 0.89 (m, 1H), 0.58 (m, 1H), 0.45 (m, 2H)

Example 196. (S)-quinuclidin-3-yl(6′-(2-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35˜7.25 (m, 3H), 7.15 (m, 1H), 7.05 (m, 1H),7.03 (m, 1H), 6.97 (d, 1H), 5.15 (m, 1H), 4.76 (br, 1H), 4.33 (m, 1H),4.10 (m, 2H), 3.61 (m, 2H), 3.30˜3.24 (m, 3H), 3.25 (m, 1H), 2.85˜2.74(m, 7H), 2.05 (br, 1H), 1.94 (br, 1H), 1.80 (br, 1H), 1.70 (br, 1H),1.59 (br, 1H), 1.38 (br, 1H), 1.14 (br, 1H), 0.89 (m, 1H), 0.58 (m, 1H),0.45 (m, 2H)

Example 197. (S)-quinuclidin-3-yl(6′-(4-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32˜7.25 (m, 2H), 7.22 (d, 2H), 7.14 (m, 1H),7.08 (d, 2H), 5.22 (s, 2H), 5.13 (m, 1H), 4.77 (br, 1H), 4.37 (d, 1H),3.53 (s, 3H), 3.25 (m, 1H), 2.85˜2.67 (m, 7H), 2.05 (br, 1H), 1.95 (br,1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.10(br, 1H), 0.89 (m, 1H), 0.56 (m, 1H), 0.42 (m, 2H)

Example 198. (S)-quinuclidin-3-yl(6′-(3-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35˜7.25 (m, 3H), 7.15 (m, 1H), 6.93 (d, 1H),6.87 (s, 2H), 5.20 (s, 2H), 5.13 (m, 1H), 4.77 (br, 1H), 4.37 (d, 1H),3.51 (s, 3H), 3.25 (m, 1H), 2.85˜2.67 (m, 7H), 2.05 (br, 1H), 1.95 (br,1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.10(br, 1H), 0.89 (m, 1H), 0.56 (m, 1H), 0.42 (m, 2H)

Example 199. (S)-quinuclidin-3-yl(6′-(2-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35˜7.25 (m, 3H), 7.15 (m, 1H), 7.05 (m, 1H),7.03 (m, 1H), 5.15 (m, 1H), 5.10˜5.07 (m, 2H), 4.77 (br, 1H), 4.36 (d,1H), 3.32˜3.27 (m, 3H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.05 (br, 1H),1.94 (br, 1H), 1.80 (br, 1H), 1.70 (br, 1H), 1.59 (br, 1H), 1.38 (br,1H), 1.14 (br, 1H), 0.89 (m, 1H), 0.58 (m, 1H), 0.45 (m, 2H)

Example 200. (S)-quinuclidin-3-yl(6′-(2-chloro-4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.38 (m, 1H), 7.26 (m, 1H), 7.14 (m, 1H), 7.10(m, 1H), 7.04 (m, 1H), 6.88 (d, 1H), 5.20˜5.10 (m, 1H), 4.75 (m, 1H),4.33 (t, 1H), 3.85 (s, 3H), 3.25 (m, 1H), 2.85˜2.73 (m, 5H), 2.46 (m,2H), 2.05 (br, 1H), 1.95 (br, 1H), 1.82 (br, 1H), 1.69 (br, 1H), 1.59(br, 1H), 1.35 (br, 1H), 1.10 (br, 1H), 0.88 (m, 1H), 0.56 (m, 1H), 0.42(m, 2H)

Example 201. (S)-quinuclidin-3-yl(6′-(4-chloro-3-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.39 (d, 2H), 7.26 (m, 1H), 7.13 (m, 1H), 6.84(m, 2H), 5.14 (m, 1H), 4.75 (m, 1H), 4.35 (d, 1H), 3.91 (s, 3H), 3.25(m, 1H), 2.86˜2.63 (m, 7H), 2.00 (m, 1H), 1.95 (br, 1H), 1.75 (br, 1H),1.69 (br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.10 (br, 1H), 0.90 (m,1H), 0.58 (m, 1H), 0.45 (m, 2H)

Example 202. (S)-quinuclidin-3-yl(6′-(3-fluoro-4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35 (m, 1H), 7.26 (m, 1H), 7.14 (m, 1H), 7.06(m, 1H), 7.00 (m, 2H), 5.15 (m, 1H), 4.75 (m, 1H), 4.36 (d, 1H), 3.94(s, 3H), 3.25 (m, 1H), 2.84˜2.65 (m, 7H), 2.06 (br, 1H), 1.95 (br, 1H),1.82 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.35 (br, 1H), 1.10 (br,1H), 0.89 (m, 1H), 0.56 (m, 1H), 0.42 (m, 2H)

Example 203. (S)-quinuclidin-3-yl(6′-(3-ethylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35 (m, 2H), 7.27 (m, 1H), 7.17 (m, 1H), 7.15(m, 3H), 5.15 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 3.25 (m, 1H),2.87˜2.71 (m, 7H), 2.67 (m, 2H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br,1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.26 (t, 3H), 1.10 (m,1H), 0.90 (m, 1H), 0.59 (m, 1H), 0.45 (m, 2H)

Example 204. (S)-quinuclidin-3-yl(6′-(3-(tert-butyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.40˜7.33 (m, 4H), 7.27 (m, 1H), 7.18 (m, 1H),7.12 (d, 1H), 5.15 (m, 1H), 4.77 (br, 1H), 4.38 (d, 1H), 3.25 (m, 1H),2.87˜2.66 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H), 1.68(br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.37 (s, 9H), 1.10 (m, 1H), 0.90(m, 1H), 0.59 (m, 1H), 0.45 (m, 2H)

Example 205. (S)-quinuclidin-3-yl(6′-(3-isopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.36 (m, 2H), 7.27 (m, 2H), 7.17 (m, 2H), 7.13(d, 1H), 5.15 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 3.25 (m, 1H), 2.94(m, 1H), 2.87˜2.71 (m, 7H), 2.67 (m, 2H), 2.10 (br, 1H), 1.92 (br, 1H),1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.28 (m, 6H),1.10 (m, 1H), 0.90 (m, 1H), 0.59 (m, 1H), 0.45 (m, 2H)

Example 206. (S)-quinuclidin-3-yl(6′-(3-(difluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.51 (m, 2H), 7.43 (m, 2H), 7.38 (m, 1H), 7.27(m, 1H), 7.14 (m, 1H), 6.84˜6.55 (t, 1H), 5.15 (m, 1H), 4.77 (br, 1H),4.34 (d, 1H), 3.25 (m, 1H), 2.86˜2.60 (m, 7H), 2.10 (br, 1H), 1.92 (br,1H), 1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.10 (m,1H), 0.90 (m, 1H), 0.59 (m, 1H), 0.45 (m, 2H)

Example 207. (S)-quinuclidin-3-yl(6′-(3-(dimethylamino)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.39˜7.18 (m, 4H), 6.74 (d, 1H), 6.66 (s, 2H),5.15 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 3.25 (m, 1H), 2.97 (s, 6H),2.86˜2.60 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H), 1.68(br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.10 (m, 1H), 0.88 (m, 1H), 0.59(m, 1H), 0.44 (m, 2H)

Example 208. (S)-quinuclidin-3-yl(6′-(3-isopropoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35˜7.15 (m, 3H), 7.15 (m, 1H), 6.86 (m, 3H),5.15 (m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.35 (d, 1H), 3.25 (m, 1H),2.85˜2.68 (m, 7H), 2.08 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H), 1.68(br, 1H), 1.59 (br, 1H), 1.39 (br, 1H), 1.35 (d, 6H), 1.15 (m, 1H), 0.88(m, 1H), 0.59 (m, 1H), 0.44 (m, 2H)

Example 209. (S)-quinuclidin-3-yl(6′-(2,3-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.35 (m, 1H), 7.24 (m, 1H), 7.11 (m, 2H), 6.96(d, 1H), 6.75 (d, 1H), 5.16 (m, 1H), 4.77 (br, 1H), 4.34 (m, 1H), 3.92(s, 3H), 3.52 (s, 3H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.08 (br, 1H),1.92 (br, 1H), 1.80 (br, 1H), 1.68 (br, 1H), 1.59 (br, 1H), 1.39 (br,1H), 1.15 (m, 1H), 0.87 (m, 1H), 0.56 (m, 1H), 0.43 (m, 2H)

Example 210. (S)-quinuclidin-3-yl(6′-(2,4-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31 (m, 1H), 7.24 (m, 1H), 7.11 (m, 1H), 7.09(m, 1H), 6.56 (d, 2H), 5.16 (m, 1H), 4.76 (br, 1H), 4.34 (d, 1H), 3.86(s, 3H), 3.75 (s, 3H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.08 (br, 1H),1.92 (br, 1H), 1.80 (br, 1H), 1.68 (br, 1H), 1.59 (br, 1H), 1.39 (br,1H), 1.15 (m, 1H), 0.89 (m, 1H), 0.56 (m, 1H), 0.43 (m, 2H)

Example 211. (S)-quinuclidin-3-yl(6′-(2,5-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.24 (m, 1H), 7.11 (m, 1H), 6.88(m, 2H), 6.71 (m, 1H), 5.16 (m, 1H), 4.76 (br, 1H), 4.35 (d, 1H), 3.79(s, 3H), 3.71 (d, 3H), 3.25 (m, 1H), 2.85˜2.74 (m, 7H), 2.08 (br, 1H),1.92 (br, 1H), 1.80 (br, 1H), 1.68 (br, 1H), 1.59 (br, 1H), 1.39 (br,1H), 1.15 (m, 1H), 0.88 (m, 1H), 0.56 (m, 1H), 0.42 (m, 2H)

Example 212. (S)-quinuclidin-3-yl(6′-(2,6-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32 (m, 2H), 7.24 (m, 1H), 7.06 (d, 1H), 6.65(d, 2H), 5.16 (m, 1H), 4.76 (br, 1H), 4.35 (d, 1H), 3.73 (d, 6H), 3.25(m, 1H), 2.85˜2.74 (m, 7H), 2.08 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H),1.68 (br, 1H), 1.58 (br, 1H), 1.39 (br, 1H), 1.15 (m, 1H), 0.89 (m, 1H),0.56 (m, 1H), 0.40 (m, 2H)

Example 213. (S)-quinuclidin-3-yl(6′-(3,4-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33 (m, 1H), 7.24 (m, 1H), 7.18 (m, 1H), 6.92(d, 1H), 6.85 (m, 2H), 5.14 (m, 1H), 4.77 (br, 1H), 4.35 (d, 1H), 3.93(s, 3H), 3.89 (s, 3H), 3.25 (m, 1H), 2.85˜2.67 (m, 7H), 2.08 (br, 1H),1.92 (br, 1H), 1.80 (br, 1H), 1.69 (br, 1H), 1.58 (br, 1H), 1.39 (br,1H), 1.15 (m, 1H), 0.89 (m, 1H), 0.58 (m, 1H), 0.46 (m, 2H)

Example 214. (S)-quinuclidin-3-yl(6′-(3,5-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.24 (m, 1H), 7.17 (m, 1H), 6.47(s, 1H), 6.44 (d, 2H), 5.16 (m, 1H), 4.76 (br, 1H), 4.35 (d, 1H), 3.82(s, 6H), 3.25 (m, 1H), 2.85˜2.67 (m, 7H), 2.08 (br, 1H), 1.92 (br, 1H),1.80 (br, 1H), 1.69 (br, 1H), 1.59 (br, 1H), 1.39 (br, 1H), 1.15 (m,1H), 0.89 (m, 1H), 0.58 (m, 1H), 0.45 (m, 2H)

Example 215. (S)-quinuclidin-3-yl(6′-(4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32 (m, 1H), 7.22 (m, 3H), 7.14 (m, 1H), 6.96(m, 2H), 5.15 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 3.86 (s, 3H), 3.25(m, 1H), 2.87˜2.71 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H),1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.10 (m, 1H), 0.90 (m, 1H),0.59 (m, 1H), 0.44 (m, 2H)

Example 216. (S)-quinuclidin-3-yl(6′-(3-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (t, 2H), 7.24 (m, 1H), 7.17 (m, 1H), 6.88(m, 2H), 6.84 (s, 1H), 5.15 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 3.86(s, 3H), 3.25 (m, 1H), 2.87˜2.71 (m, 7H), 2.10 (br, 1H), 1.97 (br, 1H),1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.10 (m, 1H),0.89 (m, 1H), 0.59 (m, 1H), 0.45 (m, 2H)

Example 217. (S)-quinuclidin-3-yl(6′-(4-ethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31 (m, 1H), 7.25 (m, 3H), 7.14 (m, 1H), 6.94(d, 2H), 5.15 (m, 1H), 4.77 (br, 1H), 4.34 (d, 1H), 4.07 (m, 2H), 3.25(m, 1H), 2.87˜2.71 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H),1.68 (br, 1H), 1.59 (m, 1H), 1.47 (t, 3H), 1.40 (br, 1H), 1.10 (m, 1H),0.90 (m, 1H), 0.59 (m, 1H), 0.44 (m, 2H)

Example 218. (S)-quinuclidin-3-yl(6′-(3-ethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33 (m, 2H), 7.24 (m, 1H), 7.15 (m, 1H), 6.89(m, 2H), 6.83 (s, 1H), 5.15 (m, 1H), 4.77 (br, 1H), 4.35 (d, 1H), 4.05(m, 2H), 3.25 (m, 1H), 2.87˜2.71 (m, 7H), 2.10 (br, 1H), 1.98 (br, 1H),1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.45 (t, 3H), 1.40 (br, 1H),1.10 (m, 1H), 0.89 (m, 1H), 0.59 (m, 1H), 0.45 (m, 2H)

Example 219. (S)-quinuclidin-3-yl(6′-(4-isopropoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.32 (m, 1H), 7.24 (m, 1H), 7.21 (d, 2H), 7.13(m, 1H), 6.93 (d, 2H), 5.15 (m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34(d, 1H), 3.25 (m, 1H), 2.87˜2.71 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H),1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.38 (d, 6H),1.15 (m, 1H), 0.89 (m, 1H), 0.58 (m, 1H), 0.44 (m, 2H)

Example 220. (S)-quinuclidin-3-yl(6′-(4-propoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.33 (m, 1H), 7.23 (m, 3H), 7.15 (m, 1H), 6.95(d, 2H), 5.15 (m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34 (d, 1H), 3.95(m, 2H), 3.25 (m, 1H), 2.87˜2.71 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H),1.85 (m, 2H), 1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H),1.38 (d, 6H), 1.15 (m, 1H), 1.06 (t, 3H), 0.88 (m, 1H), 0.58 (m, 1H),0.44 (m, 2H)

Example 221. (S)-quinuclidin-3-yl(6′-(4-ethylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.26 (m, 5H), 7.14 (m, 1H), 5.15(m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34 (d, 1H), 3.25 (m, 1H),2.87˜2.71 (m, 7H), 2.67 (m, 2H), 2.10 (br, 1H), 1.92 (br, 1H), 1.85 (m,2H), 1.80 (br, 1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.26 (t,3H), 1.15 (m, 1H), 1.06 (t, 3H), 0.88 (m, 1H), 0.58 (m, 1H), 0.44 (m,2H)

Example 222. (S)-quinuclidin-3-yl(6′-(4-propylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.26 (m, 5H), 7.14 (m, 1H), 5.15(m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34 (d, 1H), 3.25 (m, 1H),2.87˜2.71 (m, 7H), 2.62 (m, 2H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br,1H), 1.70 (m, 2H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.26 (t,3H), 1.15 (m, 1H), 1.01 (t, 3H), 0.88 (m, 1H), 0.58 (m, 1H), 0.44 (m,2H)

Example 223. (S)-quinuclidin-3-yl(6′-(4-isopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.26 (m, 5H), 7.14 (m, 1H), 5.15(m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34 (d, 1H), 3.25 (m, 1H), 2.96(m, 1H), 2.87˜2.68 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H),1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.28 (d, 6H), 1.15 (m, 1H),0.88 (m, 1H), 0.58 (m, 1H), 0.44 (m, 2H)

Example 224. (S)-quinuclidin-3-yl(6′-(4-isobutylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.27 (m, 1H), 7.15 (m, 5H), 5.15(m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34 (d, 1H), 3.25 (m, 1H),2.87˜2.68 (m, 7H), 2.52 (d, 2H), 2.10 (br, 1H), 1.92 (m, 2H), 1.80 (br,1H), 1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.15 (m, 1H), 0.92 (d,6H), 0.88 (m, 1H), 0.58 (m, 1H), 0.44 (m, 2H)

Example 225. (S)-quinuclidin-3-yl(6′-(4-(tert-butyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.44 (d, 2H), 7.34 (m, 1H), 7.23 (m, 3H), 7.15(m, 1H), 5.15 (m, 1H), 4.77 (br, 1H), 4.57 (m, 1H), 4.34 (d, 1H), 3.25(m, 1H), 2.87˜2.68 (m, 7H), 2.10 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H),1.68 (br, 1H), 1.59 (m, 1H), 1.40 (br, 1H), 1.35 (s, 9H), 1.15 (m, 1H),0.92 (d, 6H), 0.88 (m, 1H), 0.58 (m, 1H), 0.44 (m, 2H)

Example 226. (S)-quinuclidin-3-yl(6′-(4-cyclopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.34 (m, 1H), 7.27 (m, 1H), 7.19 (m, 2H), 7.10(m, 3H), 5.15 (m, 1H), 4.77 (br, 1H), 4.36 (d, 1H), 3.25 (m, 1H),2.85˜2.68 (m, 7H), 2.08 (br, 1H), 1.92 (br, 1H), 1.80 (br, 1H), 1.68(br, 1H), 1.59 (br, 1H), 1.39 (br, 1H), 1.35 (d, 6H), 1.15 (m, 1H), 1.00(m, 2H), 0.88 (m, 1H), 0.75 (m, 2H), 0.59 (m, 1H), 0.44 (m, 2H)

Examples 227 to 232

The titled compounds of Examples 227 to 232 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(6-bromo-7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateprepared in Preparation 7; and the corresponding substituted-boronicacids, respectively.

Example 227. (S)-quinuclidin-3-yl(7-fluoro-6-(3-fluoro-4-methoxyphenyll)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.27 (m, 2H), 7.10 (d, 1H), 7.02 (m, 2H), 4.92(m, 1H), 4.80 (m, 1H), 4.61 (d, 1H), 3.92 (s, 3H), 3.27 (m, 1H),2.92˜2.66 (m, 7H), 2.08 (br, 1H), 1.95 (br, 1H), 1.82 (m, 2H), 1.68 (br,1H), 1.60 (br, 1H), 1.42 (br, 1H), 1.05 (m, 3H), 0.90 (m, 3H)

Example 228. (S)-quinuclidin-3-yl(6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.17 (s, 2H), 7.12 (d, 1H), 7.04 (m, 1H), 4.88(m, 1H), 4.81 (m, 1H), 4.63 (d, 1H), 3.77 (m, 2H), 3.27 (m, 1H),2.95˜2.68 (m, 7H), 2.35 (s, 6H), 2.12 (br, 1H), 1.93 (m, 1H), 1.85 (m,2H), 1.71 (m, 3H), 1.59 (br, 1H), 1.43 (br, 1H), 1.08 (m, 6H), 0.95 (m,3H)

Example 229. (S)-quinuclidin-3-yl(7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (d, 2H), 7.24 (m, 2H), 7.15 (d, 1H), 7.06(m, 1H), 4.92 (m, 1H), 4.81 (m, 1H), 4.64 (d, 1H), 3.27 (m, 1H),2.94˜2.69 (m, 7H), 2.62 (m, 2H), 2.14 (br, 2H), 1.85 (br, 1H), 1.70 (m,5H), 1.60 (br, 1H), 1.42 (br, 1H), 1.07 (m, 3H), 0.99 (m, 6H)

Example 230. (S)-quinuclidin-3-yl(7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42 (d, 2H), 7.21 (d, 2H), 7.16 (d, 1H), 7.05(m, 1H), 4.91 (m, 1H), 4.79 (m, 1H), 4.66 (d, 1H), 3.30 (m, 1H),2.95˜2.72 (m, 7H), 2.53 (d, 2H), 2.12 (br, 2H), 1.90 (m, 1H), 1.85 (br,1H), 1.71 (m, 3H), 1.59 (br, 1H), 1.43 (br, 1H), 1.08 (m, 3H), 0.93 (m,9H)

Example 231. (S)-quinuclidin-3-yl(6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.14 (d, 1H), 7.18 (d, 1H), 7.09 (m, 1H), 7.00(br, 1H), 6.82 (s, 1H), 4.91 (m, 1H), 4.79 (m, 1H), 4.64 (d, 1H), 3.28(m, 1H), 2.95˜2.69 (m, 7H), 2.11 (br, 1H), 1.94 (br, 1H), 1.84 (br, 1H),1.72 (m, 3H), 1.60 (br, 1H), 1.42 (br, 1H), 1.07 (m, 3H), 0.94 (m, 3H)

Example 232. (S)-quinuclidin-3-yl(7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.45 (d, 2H), 7.13 (d, 1H), 7.05 (m, 1H), 6.59(d, 2H), 4.91 (m, 1H), 4.81 (m, 1H), 4.64 (m, 2H), 3.28 (m, 1H),2.97˜2.69 (m, 7H), 2.12 (br, 1H), 1.84 (br, 1H), 1.71 (m, 3H), 1.60 (br,1H), 1.43 (br, 1H), 1.38 (d, 6H), 1.07 (m, 3H), 0.94 (m, 3H)

Examples 233 to 238

The titled compounds of Examples 233 to 238 were prepared in accordancewith the same procedures as in Example 1, using (S)-quinuclidin-3-yl(6-bromo-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamateprepared in Preparation 8; and the corresponding substituted-boronicacids, respectively.

Example 233. (S)-quinuclidin-3-yl(6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.31 (m, 1H), 7.22 (m, 1H), 6.99 (m, 2H), 6.83(d, 1H), 4.90 (m, 1H), 4.82 (m, 1H), 4.61 (d, 1H), 3.92 (s, 3H), 3.77(d, 3H), 3.25 (m, 1H), 2.95˜2.77 (m, 7H), 2.09 (br, 2H), 1.86 (br, 2H),1.67 (br, 1H), 1.57 (br, 1H), 1.41 (br, 1H), 1.08 (m, 3H), 0.99 (m, 3H)

Example 234. (S)-quinuclidin-3-yl(6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.12 (s, 2H), 7.00 (s, 1H), 6.84 (d, 1H), 4.84(m, 1H), 4.81 (m, 1H), 4.60 (d, 1H), 3.75 (m, 3H), 3.26 (m, 1H),2.89˜2.76 (m, 7H), 2.31 (s, 6H), 2.08 (br, 1H), 1.85 (m, 3H), 1.68 (m,3H), 1.56 (br, 1H), 1.40 (br, 1H), 1.10 (t, 3H), 1.05 (m, 3H), 0.99 (m,3H)

Example 235. (S)-quinuclidin-3-yl(7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42 (d, 2H), 7.21 (d, 2H), 7.03 (s, 1H), 6.84(d, 1H), 4.83 (m, 1H), 4.81 (m, 1H), 4.63 (d, 1H), 3.75 (d, 3H), 3.27(m, 1H), 2.90˜2.78 (m, 7H), 2.63 (m, 2H), 2.11 (br, 2H), 1.85 (br, 1H),1.70 (m, 5H), 1.60 (br, 1H), 1.43 (br, 1H), 1.06 (m, 3H), 0.96 (m, 6H)

Example 236. (S)-quinuclidin-3-yl(6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42 (d, 2H), 7.15 (d, 2H), 7.06 (s, 1H), 6.86(d, 1H), 4.87 (m, 1H), 4.73 (m, 1H), 4.64 (d, 1H), 3.78 (d, 3H), 3.28(m, 1H), 2.89˜2.79 (m, 7H), 2.51 (d, 2H), 2.12 (br, 2H), 1.90 (m, 1H),1.82 (br, 1H), 1.68 (m, 3H), 1.56 (br, 1H), 1.42 (br, 1H), 1.06 (m, 3H),0.99 (m, 3H), 0.95 (d, 6H)

Example 237. (S)-quinuclidin-3-yl(6-(2-(tert-butoxy)pyridin-4-yl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 8.12 (d, 1H), 7.07 (s, 1H), 7.01 (br, 1H),6.88 (d, 1H), 6.81 (s, 1H), 4.82 (m, 1H), 4.73 (m, 1H), 4.62 (d, 1H),3.77 (d, 3H), 3.27 (m, 1H), 2.86˜2.74 (m, 7H), 2.11 (br, 1H), 1.94 (br,1H), 1.84 (br, 1H), 1.77 (m, 3H), 1.60 (s, 9H), 1.43 (br, 1H), 1.08 (m,3H), 0.99 (m, 3H)

Example 238. (S)-quinuclidin-3-yl(6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate

¹H-NMR (400 MHz, CDCl₃) δ 7.42 (d, 2H), 7.04 (s, 1H), 6.92 (d, 2H), 683(d, 1H), 4.86 (m, 1H), 4.80 (m, 1H), 4.70 (m, 1H), 4.60 (m, 1H), 3.79(d, 3H), 3.26 (m, 1H), 2.88˜2.76 (m, 7H), 2.12 (br, 1H), 1.86 (br, 1H),1.68 (m, 3H), 1.58 (br, 1H), 1.42 (br, 1H), 1.36 (d, 6H), 1.05 (m, 3H),1.00 (m, 3H)

Experimental Example 1: Evaluation of Inhibitory Activities Against GCS

The inhibitory activities of the compounds of the present inventionagainst GCS were evaluated, as follows, according to the methoddescribed in the known literature (Hayashi Y et al., A sensitive andreproducible assay to measure the activity of glucosylceramide synthaseand lactosylceramide synthase using HPLC and fluorescent substrates,Analytical Biochemistry 345 (2005) 181-186). Ibiglustat, known as a GCSinhibitor, was used as a control.

(1) Materials

A549 cells (ATCC, CCL-185)

NBD C6-ceramide (Thermo Fisher, N1154)

UDP-glucose (Sigma, U4625)

Potassium chloride (Sigma, P9333)

UltraPure™ 0.5 M EDTA (Invitrogen, 15575-038)

BCA protein assay kit (Thermo Fisher, 23227)

Ibiglustat (Shanghai Systeam Biochem Co., ltd, Genz-682452)

HEPES (sigma, H3375)

Protease/phosphatase inhibitor cocktail (CST, 5872s)

DMEM (GIBCO, 11995-065)

FBS (GIBCO, 16000-044)

Antibiotic-Antimycotic (100×) (GIBCO, 15240-112)

200 mM L-glutamine (GIBCO, 25030081)

PBS (GIBCO, 10010-023)

0.25% Trypsin-EDTA (GIBCO, 25200-056)

Dimethyl sulfoxide (Sigma, 34869)

2-propanol, HPLC grade (Burdick & Jackson, AH323-4)

Hexane, HPLC grade (Burdick & Jackson, AH216-4)

Chloroform (Sigma, C2432)

Methanol (Merck, 1.06009.1011)

(2) Protocol

<1> Preparation of Cell Lysates

A549 cells (ATCC, CCL-185) were cultured in a DMEM medium supplementedwith 10% fetal bovine serum (FBS), 1× antibiotic-antimycotic, and1×L-glutamine, in an incubator at 37° C. and 5% CO₂. After the cellsattached to the culture dish were washed with phosphate buffered saline(PBS), the cells were scraped off with a cell scraper and thencentrifuged (4000 rpm, 3 min, 4° C.) to collect the cells in a 50 mltube. The cell pellets were suspended in a lysis buffer (50 mM HEPES, pH7.3, containing 1× the protease/phosphatase inhibitor cocktail), lysedby sonication, and then the lysate was centrifuged (13000 rpm, 10 min,4° C.). The obtained supernatant was used for the quantitative analysisof proteins. The amount of proteins was measured using the BCA proteinassay kit, using bovine serum albumin as a standard.

<2> GCS Enzyme Reaction

Enzymatic reactions were initiated by sequentially adding the followingreaction materials to a 96 deep-well plate. Thereafter, the enzymaticreactions were performed at 37°° C. for 90 minutes.

Enzyme reaction mix (Total 50 ul) Stock Con. Final Con. Volume (ul) 1Cpd. Mix Cpd. 500~0.003 10000~0.056 nM 1 uM (DMSO) Total 1 2 Sub Mix 20mM UDP-Glc 500 uM 1.25 25 mM EDTA 1 mM 2 500 uM 5 uM 0.5 NBD-Cer/BSA D.W35.25 Total 39 3 Enzyme 3.135 ug/ul 0.627 ug/ul(31.35 ug) 10 Mix A549cell lysate Total 10

<3> Lipid Extraction

The enzymatic reactions were stopped by adding 100 μl ofchloroform/methanol (2:1, v/v). After vortexing for 15 seconds, eachmixture was centrifuged (4000 rpm, 10 min, 18° C.). The lower layer (50μl) was transferred to a new 96 deep-well plate and dried with a reducedconcentrator.

<4> HPLC Analysis

Lipids were dissolved in 100 μl of isopropyl alcohol/n-hexane/H₂O(55:44:1, v/v/v) and then transferred to a glass vial for HPLC (Agilent,8004-HP-H/i3u). The sample (100 μl) was automatically loaded onto anormal-phase column (Intersil SIL 150A-5, 4.6×250 mm, GL Sciences,Japan) and then eluted at a flow rate of 2.0 ml/min with isopropylalcohol/n-hexane/H₂O (55:44:1, v/v/v). The fluorescence thereof wasmeasured with a fluorescence detector (Agilent, 1260 FLD Spectra), using470 nm and 530 nm as excitation and emission wavelengths, respectively.

<5> Data Analysis

Data analysis was performed by the following equations.

% Area (Sample)=Area (GlcCer)/[Area (Cer)+Area (GlcCer)]×100

% GCSactivity=[Area(Sample)−Area(ibiglustat)]/[Area(DMSO)−Area(ibiglustat)]×100

The obtained % GCS activity data was analyzed with the software GraphPadPrism (Ver 5.01) to calculate the IC₅₀ values. The results are shown inTables 1 and 2 below.

TABLE 1 Example IC₅₀ (nM) 1 6.78 2 3.04 3 2.3 4 1.417 5 0.989 6 0.697 71.69 8 2.1 9 2.65 10 2.56 11 8.18 12 9.28 13 23.55 14 8.8 15 6.88 163.96 17 5.75 18 5.41 19 3.44 20 7.16 21 2.53 22 8.42 23 1.8 24 9.1 25 1526 6.61 27 2.49 28 1.33 29 8.52 30 7.93 31 6.58 32 8.31 33 3.95 34 6.135 9.16 36 22.43 37 5.07 38 1.7 39 2.88 40 1.77 41 9.08 42 6.71 43 6.0644 7.59 45 21.31 46 12.96 47 2.52 48 3.02 49 35.01 50 33.46 51 9.42 5231.75 53 86.44 54 61.83 55 34.15 57 23.4 58 10.85 59 18.95 60 106.5 618.48 62 7.37 63 6.7 64 13.03 65 14.2 66 46.94 67 7.3 68 63.48 69 40.4770 83.93 71 22.8 72 66.04 73 359 74 14.43 75 22.69 76 18.73 77 74.94 7830.1 79 12.94 80 15.45 81 63.26 82 30.26 83 39.12 84 75.63 85 74.3 862.6 87 6 88 3.5 89 2.2 90 1.01 91 0.81 92 1.04 93 1.76 94 0.97 95 0.8596 1.79 97 0.86 98 1.7 99 1.65 100 1.78 101 1.59 102 1 103 0.95 104 2.25105 1.39 106 4.05 107 5.86 108 2.55 109 2.89 110 0.64 111 2.36 112 3.75113 0.94 114 1.8 115 1.17 116 8.62 117 30.27 118 17.02 119 11.16 1205.65 121 5.51

TABLE 2 Example IC₅₀ (nM) 122 3.38 123 0.97 124 1.6 125 1.1 126 0.83 1271.92 128 2.84 129 2.08 130 1.24 131 1.49 132 1.16 133 1.05 134 2.95 1352.81 136 9.22 137 2.14 138 1.19 139 4.78 140 1.49 141 1.51 142 1.11 1431.44 144 1.39 145 0.87 146 1.8 147 1 148 3.21 149 3.5 150 8.7 151 7.27152 5.72 153 4.43 154 8.4 155 20.97 156 19.56 157 32.24 158 34.23 15910.87 160 14.54 161 26.52 162 10.55 163 15.3 164 9.23 165 18.4 166 56.23167 19.55 168 17.88 169 40.91 170 9.41 171 5.33 172 4.83 173 1.61 1744.35 175 14.8 176 14.92 177 23.48 178 22.73 179 10 180 9.54 181 12.7 18211.92 183 12.92 184 7.52 185 14.78 186 24.4 187 13.9 188 16.1 189 18.9190 11.9 191 9.9 192 12.9 193 20.9 194 1.03 195 5.39 196 6.02 197 3.13198 5.17 199 7.24 200 8.85 201 33.46 202 1.16 203 13.53 204 38.39 20534.2 206 10.17 207 23.21 208 21.2 209 15.24 210 23.65 211 27.57 212104.2 213 34.20 214 32.56 215 2.35 216 12.20 217 1.01 218 19.79 219 1.1220 0.63 221 2.01 222 0.75 223 2.4 224 1.53 225 6.55 226 0.93 227 0.5228 1.34 229 0.31 230 0.3 231 0.86 232 0.29 233 0.65 234 1.45 235 0.19236 0.53 237 1.84 238 0.55

From the results of Tables 1 and 2, it can be seen that the compounds ofthe present invention exhibit excellent inhibitory activity against GCS.

Experimental Example 2: Evaluation of Inhibitory Activities Against GM1Production

GM1, which is the final product of sphingolipid metabolism, is expressedon the cell membrane and thus the detection thereof is easy. Inaddition, the amount of GM1 represents the conversion of ceramide toglucosylceramide. Therefore, the inhibitory activities of the compoundsof the present invention against GM1 production were evaluated, asfollows, according to the method described in the known literature(Dijkhuis et al., Gangliosides do not affect ABC transporter function inhuman neuroblastoma cells. The Journal of Lipid Research 47 (2006).1187-1195). Ibiglustat, known as a GCS inhibitor, was used as a control.

(1) Materials

Jurkat cells, Clone E6-1 (ATCC, TIB-152)

Cholera toxin subunit B (CTB), FITC (Sigma, C1655)

Ibiglustat (Shanghai Systeam Biochem Co., ltd, Genz-682452)

DMSO (Sigma, D2650)

Fixation buffer (BD, 554655)

RPMI 1640 (Gibco, A1049101)

FBS (Gibco, 16000-044)

Antibiotic-Antimycotic (100×) (Gibco, 15240-122)

FACS Sheath Fluid (BD, 342003)

Jurkat cells were cultured in RPMI 1640 medium supplemented with 10% FBSand 1× Antibiotic-Antimycotic. A washing solution was prepared by adding10 ml of FBS to 490 ml of FACS Sheath Fluid. The CTB-FITC solution wasprepared by diluting the CTB-FITC stock solution (10 mg/ml) with thewashing solution to a final concentration of 2 μg/ml.

(2) Protocol

A cell suspension (1×10⁵ cells/ml) was prepared with the culture medium(RPMI 1640 medium supplemented with 10% FBS and 1×Antibiotic-Antimycotic). The cell suspension (200 μl) was added to eachwell of a 96-well plate (20,000 cells/well) and then the compounds weretreated thereto in a final concentration of 0.05 to 3000 nM (3 fold, 11points) per well. Each mixture was incubated in a CO₂ incubator at 37°C. for 72 hours. After centrifuging at 1500 rpm for 3 minutes to removethe medium, the cells were resuspended in 200 μl of the washing solutionper well. After centrifuging at 1500 rpm for 3 minutes to remove thewashing solution, the cells were resuspended in 200 μl of the 2 ug/mlCTB-FITC solution. The obtained suspension was incubated at 4° C. for 60minutes, while not being exposed to light. After centrifuging at 1500rpm for 3 minutes to remove the CTB-FITC solution, the cells were washedwith 200 μl of the washing solution. The washing process wasadditionally repeated twice. The washed plate was centrifuged at 1500rpm for 3 minutes to remove the washing solution and then the cells werecompletely resuspended in 200 μl of the fixation buffer. IC₅₀ wasdetermined from the values obtained by quantifying FITC fluorescenceswith Guava™ easyCyte 5HT (Merck Milipore, 0500-4005).

Data analysis was performed by the following equations.

% MFI (median fluorescence intensity)=(fluorescence value ofdrug-treated group/fluorescence value of DMSO-treated group)×100

% Cells=(cell concentration in the well/cell concentration in theDMSO-treated group)×100

% MFI and % cell data were analyzed with the software GraphPad Prism(Ver 5.01) to calculate IC₅₀ values. The results are shown in Tables 3and 4 below.

TABLE 3 Example IC₅₀ (nM) 1 62.58 2 54.5 3 58.66 4 34.93 5 27.15 6 15.827 13.59 8 12.39 9 41.32 10 37.66 11 38.45 12 19.59 13 143.4 14 61.75 1519.69 16 33.96 17 36.97 18 99.21 19 67.39 20 84.36 21 42.13 22 22.46 2327.68 24 23.14 25 45.06 26 30.84 27 30.29 28 5.312 29 155.5 30 71.36 312.92 32 474.9 33 498.6 34 297.9 35 265 36 338.6 37 286 38 316.3 39 849.440 218.2 41 291.5 42 209.6 43 615.8 44 480.3 45 152.1 46 216.5 47 432.948 362 49 411.5 50 2189 51 426 52 22.7 53 313.7 54 216.3 55 109.6 5781.2 58 73.54 59 153.3 61 61.9 62 49.25 63 41.84 64 131.2 65 95.49 66102.5 67 38.3 68 276.3 69 220.1 70 133 71 95.43 72 115.8 73 587.1 7454.38 75 138.1 76 156.2 77 197.1 78 230.1 79 65.33 80 225.2 81 410 8214.36 83 386.5 84 144.3 85 192.3 86 14.18 87 19.52 88 11.27 89 7.791 904.889 91 2.863 92 2.718 93 0.3883 94 3.105 95 0.123 96 3.294 97 1.385 982.048 99 2.558 100 2.589 101 2.548 102 1.432 103 0.9972 104 2.272 1050.2097 106 3.332 107 6.502 108 6.7 109 2.972 110 0.2896 111 1.838 1120.8019 113 0.9638 114 1.275 115 0.5598 116 7.76 117 37.81 118 12.36 1191.862 120 1.83 121 0.0387 122 0.7739

TABLE 4 Example IC₅₀ (nM) 123 1.43 124 3.35 125 2.041 126 1.887 127 2128 1.3 129 1.3 130 1.3 131 2.3 132 2 133 1 134 6.6 135 8.3 136 21.2 1378.4 138 3.8 139 8.8 140 1.4 141 1.1 142 3.4 143 0.5 144 1.6 145 0.7 1460.8 147 0.1 148 4.6 149 3.9 150 17.1 151 33.42 152 25.89 153 5.542 15417.73 155 108.2 156 132.4 157 119.8 158 248.9 159 49.78 160 67.68 161121.6 162 57.37 163 55.12 164 26.07 165 24.3 166 392.10 167 102.70 16870.73 169 442.50 170 38.99 171 94.89 172 67.89 173 18.93 174 39.32 175167.2 176 211.2 177 169.6 178 274 179 115.2 180 99.06 181 91.71 18240.36 183 145 184 86.95 185 72.95 186 79.81 187 35.45 188 34.07 18925.12 190 19.9 191 14.45 192 14.02 193 21.58 194 7.922 195 23.32 19625.21 197 2.801 198 8.684 199 7.634 200 45.99 201 111 202 24.45 203 35204 92.90 205 44.3 206 15.2 207 57.3 208 47.7 209 47 210 44.2 211 147.2212 220.6 213 145.0 214 62.3 215 57.3 216 115.20 217 15.8 218 63.30 21916 220 6.7 221 18.8 222 9.3 223 24.1 224 6.7 225 22.4 226 10.8 227 12.8228 12.5 229 1.7 230 1.8 231 3.8 232 2.7 233 21.7 234 14.9 235 3.2 2363.2 237 18.8 238 3.5

From the results of Tables 3 and 4, it can be seen that the compounds ofthe present invention exhibit excellent inhibitory activity against GM1production.

1. A compound of Formula 1 or pharmaceutically acceptable salt thereof:

wherein, L is —O—, —CO—, —CR₁R₂—, or —NR₃—, R₁ and R₂ are, independentlyeach other, hydrogen; halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl having anitrogen, oxygen, or sulfur atom; C₃˜C₁₀ cycloalkyl; 3- to 12-memberedheterocyclic; or C₁˜C₆ alkoxy, R₃ is hydrogen; C₁˜C₆ alkyl; C₁˜C₆ alkylhaving a nitrogen, oxygen, or sulfur atom; C₃˜C₁₀ cycloalkyl; 3- to12-membered heterocyclic; or C₁˜C₆ alkoxy, X is hydrogen; halogen; C₁˜C₆alkyl; C₁˜C₆ alkyl substituted with 1 to 3 halogens; C₁˜C₆ alkyl havinga nitrogen, oxygen, or sulfur atom; C₁˜C₆ alkoxy; or C₁˜C₆ alkoxysubstituted with 1 to 3 halogens, Y, Q and Z are, independently eachother, —CR₄R₅—, R₄ and R₅ are, independently each other, hydrogen;halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl having a nitrogen, oxygen, or sulfuratom; C₃˜C₁₀ cycloalkyl; 3- to 12-membered heterocyclic; or C₁˜C₆alkoxy; or R₄ and R₅ form C₃˜C₁₀ cycloalkyl together with the carbonatom of Y, Q or Z to which they are attached, W is a bond, —CH₂—, —O—,—NH—, —CH₂CH₂—, —CH═CH—, or —C≡C—, A ring is 6- to 12-membered aryl; 5-to 12-membered heteroaryl; C₃˜C₁₀ cycloalkyl; or 3- to 12-memberedheterocyclic, and X₁, X₂, X₃, and X₄ are, independently each other,hydrogen; cyano; halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl substituted with 1 to3 halogens; C₃˜C₁₀ cycloalkyl; 3- to 12-membered heterocyclic; C₁˜C₆alkoxy; C₁˜C₆ alkoxy-C₁˜C₆ alkoxy; C₁˜C₆ alkoxy substituted with 1 to 3halogens; C₁˜C₆ alkylthio; morpholinyl; amino; mono- or di-C₁˜C₆alkylamino; C₁˜C₆ alkylcarbonyl; hydroxy; or nitro.
 2. The compound orpharmaceutically acceptable salt thereof as claimed in claim 1, whereinL is —O—.
 3. The compound or pharmaceutically acceptable salt thereof asclaimed in claim 1, wherein X is hydrogen; halogen; or C₁˜C₆ alkoxy. 4.The compound or pharmaceutically acceptable salt thereof as claimed inclaim 1, wherein R₄ and R₅ are, independently each other, hydrogen orC₁˜C₆ alkyl; or R₄ and R₅ form C₃˜C₁₀ cycloalkyl together with thecarbon atom of Y, Q or Z to which they are attached.
 5. The compound orpharmaceutically acceptable salt thereof as claimed in claim 1, whereinY is —CH₂—.
 6. The compound or pharmaceutically acceptable salt thereofas claimed in claim 1, wherein Q is —CH₂—.
 7. The compound orpharmaceutically acceptable salt thereof as claimed in claim 1, whereinY is —CH₂—; Q is —CH₂—; and Z is —CR₄R₅—; and R₄ and R₅ are,independently each other, hydrogen or C₁˜C₆ alkyl; or R₄ and R₅ form beC₃˜C₁₀ cycloalkyl together with the carbon atom of Z.
 8. The compound orpharmaceutically acceptable salt thereof as claimed in claim 1, whereinW is a bond.
 9. The compound or pharmaceutically acceptable salt thereofas claimed in claim 1, wherein the A ring is phenyl, benzodioxolyl,2,3-dihydrobenzodioxinyl, 2,3-dihydrobenzofuranyl, pyridinyl,pyrrolo[2.3-b]pyridinyl, pyrimidinyl, or thiophenyl.
 10. The compound orpharmaceutically acceptable salt thereof as claimed in claim 1, whereinX₁, X₂, X₃, and X₄ are, independently each other, hydrogen; cyano;halogen; C₁˜C₆ alkyl; C₁˜C₆ alkyl substituted with 1 to 3 halogens;C₃˜C₁₀ cycloalkyl; C₁˜C₆ alkoxy; C₁˜C₆ alkoxy-C₁˜C₆ alkoxy; C₁˜C₆ alkoxysubstituted with 1 to 3 halogens; morpholinyl; mono- or di-C₁˜C₆alkylamino; or C₁˜C₆ alkylcarbonyl.
 11. The compound or pharmaceuticallyacceptable salt thereof as claimed in claim 1, wherein L is —O—, X ishydrogen; halogen; or C₁˜C₆ alkoxy, R₄ and R₅ are, independently eachother, hydrogen or C₁˜C₆ alkyl; or R₄ and R₅ form C₃˜C₁₀ cycloalkyltogether with the carbon atom of Y, Q or Z to which they are attached, Wis a bond, A ring is phenyl, benzodioxolyl, 2,3-dihydrobenzodioxinyl,2,3-dihydrobenzofuranyl, pyridinyl, pyrrolo[2.3-b]pyridinyl,pyrimidinyl, or thiophenyl, and X₁, X₂, X₃, and X₄ are, independentlyeach other, hydrogen; cyano; halogen; C₁˜C₆ alkyl; C₁˜C₆ alkylsubstituted with 1 to 3 halogens; C₃˜C₁₀ cycloalkyl; C₁˜C₆ alkoxy; C₁˜C₆alkoxy-C₁˜C₆ alkoxy; C₁˜C₆ alkoxy substituted with 1 to 3 halogens;morpholinyl; mono- or di-C₁˜C₆ alkylamino; or C₁˜C₆ alkylcarbonyl. 12.The compound or pharmaceutically acceptable salt thereof as claimed inclaim 11, wherein Y is —CH₂—.
 13. The compound or pharmaceuticallyacceptable salt thereof as claimed in claim 11, wherein Q is —CH₂—. 14.The compound or pharmaceutically acceptable salt thereof as claimed inclaim 11, wherein Y is —CH₂—; Q is —CH₂—; and Z is —CR₄R₅—; and R₄ andR₅ are, independently each other, hydrogen or C₁˜C₆ alkyl; or R₄ and R₅form be C₃˜C₁₀ cycloalkyl together with the carbon atom of Z.
 15. Thecompound or pharmaceutically acceptable salt thereof as claimed in claim1, which is selected from the group consisting of: (S)-quinuclidin-3-yl(6-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(difluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,3-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-butylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-isobutylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-cyclopropyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(tert-butyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-isopropylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-ethylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,3-dihydrobenzofuran-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-morpholinophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluoropyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-methoxypyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(pyrimidin-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-(chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-(fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2,4-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3,5-difluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2,5-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(pyridin-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(o-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-(2-methoxyethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-methoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-ethoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-propoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-isopropoxyphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(benzo[d]dioxol-5-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(m-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,4-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,4-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(2,4,5-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(2,3,4-trifluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-methoxypyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-methylpyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-fluoropyridin-4-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-6-(2-(trifluoromethyl)pyridin-4-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-chloro-3-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-ethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(tert-butyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-isopropylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate(S)-quinuclidin-3-yl(6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2,6-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,4-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-chloro-4-ethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-chloro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-dimethyl-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-chloro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-acetylthiophen-3-yl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(3-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(2,2-dimethyl-7-(2-(p-tolyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-(difluoromethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(3-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7′-(4-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(4-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(4-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(4-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(3-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(3-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(3-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(3-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(2-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(2-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(2-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(2-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(p-tolyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(4-(difluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7′-(4-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-fluorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-chlorophenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-(trifluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-(trifluoromethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2-(2-methoxyethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2-(methoxymethoxy)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2-chloro-4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-chloro-3-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-fluoro-4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-ethylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate(S)-quinuclidin-3-yl(6′-(3-(tert-butyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-isopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-(difluoromethyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-(dimethylamino)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-isopropoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2,3-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2,4-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2,5-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(2,6-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3,4-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3,5-dimethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-methoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-ethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(3-ethoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-isopropoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-propoxyphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-ethylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-propylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-isopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-isobutylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-(tert-butyl)phenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(6′-(4-cyclopropylphenyl)-3′,4′-dihydro-1′H-spiro[cyclopropane-1,2′-naphthalen]-1′-yl)carbamate;(S)-quinuclidin-3-yl(7-fluoro-6-(3-fluoro-4-methoxyphenyll)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate(S)-quinuclidin-3-yl(6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;(S)-quinuclidin-3-yl(6-(2-(tert-butoxy)pyridin-4-yl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate;and (S)-quinuclidin-3-yl(6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate.16. A pharmaceutical composition for inhibiting glucosylceramidesynthase comprising the compound or pharmaceutically acceptable saltthereof as claimed in any one of claims 1 to 15 as an active ingredient.17. A pharmaceutical composition as claimed in claim 16, for preventingor treating Gaucher disease, Fabry disease, Tay-Sachs disease, orParkinson's disease.
 18. A method for inhibiting glucosylceramidesynthase in a mammal, which comprises administering a therapeuticallyeffective amount of the compound or pharmaceutically acceptable saltthereof as claimed in any one of claims 1 to 15 to the mammal in needthereof.